Gene Summary

Gene:GRB2; growth factor receptor bound protein 2
Aliases: ASH, Grb3-3, MST084, NCKAP2, MSTP084, EGFRBP-GRB2
Summary:The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the Sem5 gene of C.elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:growth factor receptor-bound protein 2
Source:NCBIAccessed: 30 August, 2019


What does this gene/protein do?
Show (42)
Pathways:What pathways are this gene/protein implicaed in?
Show (50)

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 30 August 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Amino Acid Sequence
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Cell Line
  • Proto-Oncogene Proteins
  • Neoplastic Cell Transformation
  • Down-Regulation
  • Western Blotting
  • Cell Movement
  • Signal Transducing Adaptor Proteins
  • AKT1
  • Messenger RNA
  • Lung Cancer
  • Molecular Sequence Data
  • Transfection
  • Cell Proliferation
  • GRB2 Adaptor Protein
  • siRNA
  • Intracellular Signaling Peptides and Proteins
  • Protein-Tyrosine Kinases
  • Protein Binding
  • MAP Kinase Signaling System
  • Cancer Gene Expression Regulation
  • Neoplasm Proteins
  • Thyroid Cancer
  • Phosphatidylinositol 3-Kinases
  • Chromosome 17
  • Biomarkers, Tumor
  • Enzyme Activation
  • Antineoplastic Agents
  • Gene Expression Profiling
  • Proteins
  • ErbB Receptors
  • Breast Cancer
  • Chronic Myelogenous Leukemia
  • ras GTPase-Activating Proteins
  • MicroRNAs
  • Apoptosis
  • Mutation
  • Fusion Proteins, bcr-abl
  • Phosphorylation
Tag cloud generated 30 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (4)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: GRB2 (cancer-related)

Liu JB, Jian T, Yue C, et al.
Chemo-resistant Gastric Cancer Associated Gene Expression Signature: Bioinformatics Analysis Based on Gene Expression Omnibus.
Anticancer Res. 2019; 39(4):1689-1698 [PubMed] Related Publications
BACKGROUND/AIM: This study aimed to identify biomarkers for predicting the prognosis of advanced gastric cancer patients who received docetaxel, cisplatin, and S-1 (DCS).
MATERIALS AND METHODS: Gene expression profiles were obtained from the Gene Expression Omnibus database (GSE31811). Gene-Ontology-enrichment and KEGG-pathway analysis were used for evaluating the biological functions of differentially-expressed genes. Protein-protein interaction (PPI) network and Kaplan-Meier survival analyses were employed to assess the prognostic values of hub genes.
RESULTS: A total of 1,486 differentially expressed genes (DEGs) were identified, including 13 up-regulated and 1,473 down-regulated genes. KEGG pathways such as metabolic pathways, cell adhesion molecules (CAMs), PI3K-Akt signaling pathway and pathways in cancer were significantly represented. In the PPI network, the top ten hub genes ranked by degree were GNG7, PLCB1, CALML5, FGFR4, GRB2, JAK3, ADCY7, ADCY9, GNAS and KDR. Five DEGs, including ANTXR1, EFNA5, GAMT, E2F2 and NRCAM, were associated with relapse-free survival and overall survival.
CONCLUSION: ANTXR1, EFNA5, GAMT, E2F2 and NRCAM are potential biomarkers and therapeutic targets for DCS treatment in GC.

Wang X, Peng J, Yang Z, et al.
Elevated expression of Gab1 promotes breast cancer metastasis by dissociating the PAR complex.
J Exp Clin Cancer Res. 2019; 38(1):27 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Breast cancer (BCa) remains as the second leading cause of cancer-related death in women worldwide. The majority of the deaths are due to its progression to metastatic BCa. Although Grb2-associated binding protein 1 (Gab1) has been implicated in tumor proliferation and metastasis in multiple tumors including colorectal cancer, hepatocellular carcinoma and ovarian cancer, whether and how it regulates BCa metastasis are still poorly understood.
METHODS: Western blot assay and immunohistochemical (IHC) staining were performed to assess expression of Gab1 in primary and metastatic BCa clinical samples. Biological function assay studies in vitro and in vivo were employed to investigate the functions of Gab1 during BCa metastasis. Co-immunoprecipitation (co-IP) assessment, western blot assay and immunofluorescence (IF) staining were carried out to investigate the underlying mechanism for the function of Gab1 on BCa metastasis.
RESULTS: In this study, we found that expression level of Gab1 was increased significantly in BCa tissue samples compared to that in benign mammary hyperplastic tissues. Furthermore, elevated expression of Gab1 was positively associated with metastasis in HER2 and TNBC subtypes of BCa. In BCa cell line MDA-MB-231 and SK-BR3 cells, stable overexpression of Gab1 promoted, while knockdown of Gab1 inhibited cell migration in vitro and metastasis in vivo. Mechanistically, overexpression of Gab1 enhanced its interaction with Par3, a key component of the polarity-associated partitioning defective (PAR) complex, leading to a dissociation of the PAR complex. Consequently, dissociated PAR complex induced epithelial-to-mesenchymal transition (EMT) for breast tumor metastasis. By restoration assessment, we found that only re-expression of a fully functional Gab1, but not a mutant Gab1 that harbors either Par3 binding-deficiency or Par1b binding-deficiency, could reverse the repressive phenotype of cell migration in vitro and metastasis in vivo due to Gab1 knockdown.
CONCLUSIONS: Our findings indicate that elevated expression of Gab1 promotes BCa metastasis by dissociating the PAR complex that leads to EMT, implicating a role of Gab1 as a potential biomarker of metastatic BCa. Moreover, inhibition of Gab1 expression might be a promising therapeutic strategy for BCa metastasis.

Beksac AT, Cumarasamy S, Falagario U, et al.
Multiparametric Magnetic Resonance Imaging Features Identify Aggressive Prostate Cancer at the Phenotypic and Transcriptomic Level.
J Urol. 2018; 200(6):1241-1249 [PubMed] Related Publications
PURPOSE: Multiparametric magnetic resonance imaging is a diagnostic tool for prostate cancer with limited data on prognostic use. We sought to determine whether multiparametric magnetic resonance could predict aggressive prostate cancer features.
MATERIALS AND METHODS: We retrospectively analyzed the records of 206 patients who underwent radical prostatectomy between 2013 and 2017. All patients had available RNA expression data on the final pathology specimen obtained from a location corresponding to a lesion location on multiparametric magnetic resonance imaging. The association between the PIRADS™ (Prostate Imaging Reporting and Data System) score and adverse pathology features were analyzed. We also performed differential transcriptomic analysis between the PIRADS groups. Factors associated with adverse pathology were analyzed using a multivariable logistic regression model.
RESULTS: Lesion size (p = 0.03), PIRADS score (p = 0.02) and extraprostatic extension (p = 0.01) associated significantly with the Decipher® score. Multivariable analysis showed that the PIRADS score (referent PIRADS 3, OR 8.1, 95% CI 1.2-57.5, p = 0.04), the Gleason Grade Group (referent 3, OR 5.6, 95% CI 1.5-21.1, p = 0.01) and prostate specific antigen (OR 1.103, 95% CI 1.011-1.203) were risk factors for adverse pathology findings. The difference between PIRADS 4 and 5 did not reach significance (OR 1.9, 95% CI 0.8-4.5, p = 0.12). However, the PI3K-AKT-mTOR, WNT-β and E2F signaling pathways were more active in PIRADS 5 than in PIRADS 4 cases.
CONCLUSIONS: The PIRADS score is associated with adverse pathology results, increased metastatic risk and differential genomic pathway activation.

Urtishak KA, Wang LS, Culjkovic-Kraljacic B, et al.
Targeting EIF4E signaling with ribavirin in infant acute lymphoblastic leukemia.
Oncogene. 2019; 38(13):2241-2262 [PubMed] Free Access to Full Article Related Publications
The poor outcomes in infant acute lymphoblastic leukemia (ALL) necessitate new treatments. Here we discover that EIF4E protein is elevated in most cases of infant ALL and test EIF4E targeting by the repurposed antiviral agent ribavirin, which has anticancer properties through EIF4E inhibition, as a potential treatment. We find that ribavirin treatment of actively dividing infant ALL cells on bone marrow stromal cells (BMSCs) at clinically achievable concentrations causes robust proliferation inhibition in proportion with EIF4E expression. Further, we find that ribavirin treatment of KMT2A-rearranged (KMT2A-R) infant ALL cells and the KMT2A-AFF1 cell line RS4:11 inhibits EIF4E, leading to decreases in oncogenic EIF4E-regulated cell growth and survival proteins. In ribavirin-sensitive KMT2A-R infant ALL cells and RS4:11 cells, EIF4E-regulated proteins with reduced levels of expression following ribavirin treatment include MYC, MCL1, NBN, BCL2 and BIRC5. Ribavirin-treated RS4:11 cells exhibit impaired EIF4E-dependent nuclear to cytoplasmic export and/or translation of the corresponding mRNAs, as well as reduced phosphorylation of the p-AKT1, p-EIF4EBP1, p-RPS6 and p-EIF4E signaling proteins. This leads to an S-phase cell cycle arrest in RS4:11 cells corresponding to the decreased proliferation. Ribavirin causes nuclear EIF4E to re-localize to the cytoplasm in KMT2A-AFF1 infant ALL and RS4:11 cells, providing further evidence for EIF4E inhibition. Ribavirin slows increases in peripheral blasts in KMT2A-R infant ALL xenograft-bearing mice. Ribavirin cooperates with chemotherapy, particularly L-asparaginase, in reducing live KMT2A-AFF1 infant ALL cells in BMSC co-cultures. This work establishes that EIF4E is broadly elevated across infant ALL and that clinically relevant ribavirin exposures have preclinical activity and effectively inhibit EIF4E in KMT2A-R cases, suggesting promise in EIF4E targeting using ribavirin as a means of treatment.

Liang K, Smith ER, Aoi Y, et al.
Targeting Processive Transcription Elongation via SEC Disruption for MYC-Induced Cancer Therapy.
Cell. 2018; 175(3):766-779.e17 [PubMed] Article available free on PMC after 18/10/2019 Related Publications
The super elongation complex (SEC) is required for robust and productive transcription through release of RNA polymerase II (Pol II) with its P-TEFb module and promoting transcriptional processivity with its ELL2 subunit. Malfunction of SEC contributes to multiple human diseases including cancer. Here, we identify peptidomimetic lead compounds, KL-1 and its structural homolog KL-2, which disrupt the interaction between the SEC scaffolding protein AFF4 and P-TEFb, resulting in impaired release of Pol II from promoter-proximal pause sites and a reduced average rate of processive transcription elongation. SEC is required for induction of heat-shock genes and treating cells with KL-1 and KL-2 attenuates the heat-shock response from Drosophila to human. SEC inhibition downregulates MYC and MYC-dependent transcriptional programs in mammalian cells and delays tumor progression in a mouse xenograft model of MYC-driven cancer, indicating that small-molecule disruptors of SEC could be used for targeted therapy of MYC-induced cancer.

Hao S, Li S, Wang J, et al.
Phycocyanin Reduces Proliferation of Melanoma Cells through Downregulating GRB2/ERK Signaling.
J Agric Food Chem. 2018; 66(41):10921-10929 [PubMed] Related Publications
As a type of functional food additive, phycocyanin is shown to have a potential antineoplastic property. However, its underlying anticancer mechanism in melanoma cells remains unknown. We previously reported a

Han L, Xiong L, Wang C, et al.
MicroRNA-128 contributes to the progression of gastric carcinoma through GAREM-mediated MAPK signaling activation.
Biochem Biophys Res Commun. 2018; 504(1):295-301 [PubMed] Related Publications
Gastric carcinoma (GC) represents the most common malignant cancer and the second leading cause of cancer death worldwide. However, the molecular mechanisms and biological progression of GC remain unknown. In this study, we found that miR-128 is a critical tumor suppressor that is downregulated in GC patients and GC cells and that GAREM is a direct downstream target of miR-128. Overexpression of miR-128 in HGC-27 and MKN-45 cells resulted in suppressed cell growth and promoted cell apoptosis through a GAREM-dependent mechanism. Moreover, the precise mechanisms underlying the antitumor effect of miR-128 in GC are at least partially due to suppressing activation of the MAPK signaling pathway, induced by suppressing GAREM expression. This study is the first to demonstrate that the miR-128-GAREM-MAPK signaling pathway forms a critical feedback loop and mediates GC development, and these findings might demonstrate a potential therapeutic strategy for GC.

Ramos J, Das J, Felty Q, et al.
NRF1 motif sequence-enriched genes involved in ER/PR -ve HER2 +ve breast cancer signaling pathways.
Breast Cancer Res Treat. 2018; 172(2):469-485 [PubMed] Related Publications
Nuclear respiratory factor 1 (NRF1) transcription factor has recently been shown to control breast cancer progression. However, mechanistic aspects by which NRF1 may contribute to susceptibility to different breast tumor subtypes are still not fully understood. Since transcriptional control of NRF1 seems to be dependent on epidermal growth factor receptor signaling, herein, we investigated the role of NRF1 in estrogen receptor/progesterone receptor negative, but human epidermal growth factor receptor 2-positive (ER/PR -ve HER2 +ve) breast cancer. We found that both mRNA and protein levels of NRF1 and its transcriptional activity were significantly higher in ER/PR -ve HER2 +ve breast cancer samples compared to normal breast tissues. This was consistent with our observation of higher NRF1 protein expression in the experimental model of HER2+ breast cancer brain metastasis. To identify network-based pathways involved in the susceptibility to the ER/PR -ve HER2 +ve breast cancer subtype, the NRF1 transcriptional regulatory genome-wide landscape was analyzed using the approach consisting of a systematic integration of ChIP DNA-seq, RNA-Microarray, NRF1 protein-DNA motif binding, signal pathway analysis, and Bayesian machine learning. Our findings show that a high percentage of known HER2+ breast cancer susceptibility genes, including EGFR, IGFR, and E2F1, are under transcriptional control of NRF1. Promoters of several genes from the KEGG HER2+ breast cancer pathway and 11 signaling pathways linked to 6 hallmarks of cancer contain the NRF1 motif. By pathway analysis, key breast cancer hallmark genes of epithelial-mesenchymal transition, stemness, cell apoptosis, cell cycle regulation, chromosomal integrity, and DNA damage/repair were highly enriched with NRF1 motifs. In addition, we found using Bayesian network-based machine learning that 30 NRF1 motif-enriched genes including growth factor receptors-FGFR1, IGF1R; E2Fs transcription factor family-E2F1, E2F3; MAPK pathway-SHC2, GRB2, MAPK1; PI3K-AKT-mTOR signaling pathway-PIK3CD, PIK3R1, PIK3R3, RPS6KB2; WNT signaling pathway-WNT7B, DLV1, DLV2, GSK3B, NRF1, and DDB2, known for its role in DNA repair and involvement in early events associated with metastatic progression of breast cancer cells, were associated with HER2-amplified breast cancer. Machine learning search further revealed that the likelihood of HER2-positive breast cancer is almost 100% in a patient with the high NRF1 expression combined with expression patterns of high E2F3, GSK3B, and MAPK1, low or no change in E2F1 and FGFR1, and high or no change in PIK3R3. In summary, our findings suggest novel roles of NRF1 and its regulatory networks in susceptibility to the ER/PR -ve HER2 +ve aggressive breast cancer subtype. Clinical confirmation of our machine learned Bayesian networks will have significant impact on our understanding of the role of NRF1 as a valuable biomarker for breast cancer diagnosis and prognosis as well as provide strong rationale for future studies to develop NRF1 signaling-based therapeutics to target HER2+ breast cancer.

Jiang W, Wei K, Pan C, et al.
MicroRNA-1258 suppresses tumour progression via GRB2/Ras/Erk pathway in non-small-cell lung cancer.
Cell Prolif. 2018; 51(6):e12502 [PubMed] Related Publications
OBJECTIVES: Lung cancer is still a disease with high morbidity and mortality in the world. MicroRNAs have been proven to act as an indispensable role in the reuse of multiple solid tumours. Although miR-1258 plays a vital role in suppressing metastasis in breast cancer and gastric cancer, the specific biological function of miR-1258 in non-small-cell lung cancer remains unclear.
METHODS: The differential expression of miR-1258 in NSCLC tissues and corresponding paracancerous tissues was detected by qRT-PCR and ISH. Flow cytometry and CCK-8, EdU, tubule formation, and senescence assays were performed, and xenograft models were studied to explore the function of miR-1258. Potential targets of miR-1258 were verified by dual luciferase reporter assay, qRT-PCR, IHC and Western blotting.
RESULTS: In vitro and in vivo gain- and loss-of-function assays suggested that miR-1258 inhibits NSCLC cell proliferation and induces senescence and apoptosis. The luciferase reporter assay, IHC and Western blotting analysis showed that GRB2 is one of the direct targets of miR-1258. The GRB2 overexpression plasmid can reverse the functional changes after overexpression of miR-1258. In contrast, miR-1258 inhibitor significantly reversed si-GRB2-induced GRB2 down-regulation. Mechanistically, overexpression of miR-1258 inhibits GRB2 expression and then leads to inactivation of the Ras/Erk oncogenic pathway.
CONCLUSIONS: Our results indicate that miR-1258 can suppress NSCLC progression by targeting the GRB2/Ras/Erk pathway, which may lead to different insights into potential biomarkers and novel therapeutic strategies for NSCLC patients.

Conti A, Luchini A, Benassi MS, et al.
Circulating Candidate Biomarkers in Giant Cell Tumors of Bone.
Proteomics Clin Appl. 2018; 12(6):e1800041 [PubMed] Related Publications
PURPOSE: Approximately 5% of giant cell tumors (GCT) of bone develop pulmonary metastases. Although many biomarkers have been proposed, identification of circulating low abundance molecules may be useful to predict malignant progression.
EXPERIMENTAL DESIGN: The hydrogel nanoparticle technique followed by MS was used to detect low molecular weight serum proteins or protein fragments in serum of 20 GCT patients with different clinical course and in ten healthy sera used as control. The most representative low-abundant de novo or differentially abundant proteins were submitted to String database that recognized interconnected activated pathways including protein activation cascade, wound healing, cell-substrate adhesion, and response to stress. Statistics were performed for identification of candidate prognostic factors.
RESULTS: Proteome cluster analysis separated metastasis-free from metastatic GCT patients in two well-defined groups where serum levels of signaling transduction mediators and regulators of kinase activity presented a high discriminatory power. Increased expression of proteins STAT5B, GRB2, and OXSR1 was related to a higher probability of metastasis. Multivariate analysis demonstrated that tumor grade and STAT5B were independent prognostic factors.
CONCLUSIONS AND CLINICAL RELEVANCE: By using a noninvasive technique, we identified differentially abundant serum candidate biomarkers, also providing prognostic information in patients with GCT of bone.

Abdel-Megeed RM, Hamed AR, Matloub AA, et al.
Regulation of apoptotic and inflammatory signaling pathways in hepatocellular carcinoma via Caesalpinia gilliesii galactomannan.
Mol Cell Biochem. 2019; 451(1-2):173-184 [PubMed] Related Publications
A polysaccharide characterized as galactomannan (GMann) with a molecular weight of 117.76 kDa was isolated from the aqueous extract of Caesalpinia gilliesii (C. gilliesii) seeds then assessed for antiproliferative potential against human hepatocellular carcinoma cell line (HepG2). Further, HCC was induced in Wister albino rats by Diethylnitrosamine (DEN) ip injection (200 mg/kg bw), and CCl4 orally (2 ml/kg bw) for two months then subjected to GMann orally treatment (2 mg/kg bw) for one month. In results, isolated GMann is constituted of sugars (89.99 ± 2.3%), moisture (6.89 ± 0.45%), ash (0.06 ± 0.2%), and protein (2.81%) and composed mainly of mannose and galactose in ratio M/G 3.79. In vitro study, data revealed a concentration-dependent potency of GMann to induce cell death of HepG2 cells with IC

Shao NY, Wang DX, Wang Y, et al.
MicroRNA-29a-3p Downregulation Causes Gab1 Upregulation to Promote Glioma Cell Proliferation.
Cell Physiol Biochem. 2018; 48(2):450-460 [PubMed] Related Publications
BACKGROUND/AIMS: Glioma causes significant human mortalities annually. Molecularly-targeted therapy is a focus of glioma research.
METHODS: Grb2-associated binding 1 (Gab1) expression and microRNA-29a-3p ("miR-29a-3p") expression in human glioma cells and tissues were tested by Western blotting assay and qRT-PCR assay. shRNA/siRNA strategy was applied to silence Gab1 in human glioma cells. miR-29a or anti-sense miR-29a construct was transfected to human glioma cells. Cell proliferation was tested by BrdU ELISA assay and cell counting assay.
RESULTS: We show that expression of Gab1 was significantly elevated in human glioma tissues and cells, which correlated with downregulation of its putative microRNA: miR-29a-3p. In A172 glioma cells and primary human glioma cells, Gab1 shRNA/siRNA inhibited Akt-Erk activation and cell proliferation. Forced-expression of miR-29a-3p downregulated Gab1, inhibiting glioma cell proliferation, whereas miR-29a-3p was in-effective on cell proliferation in Gab1-silenced A172 cells. Furthermore, introduction of a 3'-untranslated region (3'-UTR) mutant Gab1 (UTR-G160A) blocked miR-29a-3p-induced inhibition on Akt signaling and A172 cell proliferation.
CONCLUSIONS: miR-29a-3p downregulation leads to Gab1 upregulation to promote glioma cell proliferation.

Jia Y, French B, Tillman B, French S
Different roles of FAT10, FOXO1, and ADRA2A in hepatocellular carcinoma tumorigenesis in patients with alcoholic steatohepatitis (ASH) vs non-alcoholic steatohepatitis (NASH).
Exp Mol Pathol. 2018; 105(1):144-149 [PubMed] Article available free on PMC after 18/10/2019 Related Publications
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer related deaths worldwide. Among others, non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the two major risk factors as both of them may develop cirrhosis and hepatocellular carcinoma (HCC) if left untreated. However, patients with NASH progress to HCC at a rate around 0.5% annually, while 3-10% ASH patients may progress to HCC annually. The present study is to demonstrate the molecular differences in oncogenesis pathway between NASH and ASH. By using immunofluorescence study and quantitating the fluorescence intensity morphometrically in liver biopsied specimens from NASH and ASH patients, the protein expression of candidate molecules within hepatocytes cytoplasm are studied, including two HCC-related molecules FAT10 and FOXO1, and one GPCR pathway related molecule ADRA2A. Compared with the control group patients, the expression levels of all the molecules were upregulated in the ASH group of patients (p < 0.001 in all molecules), while FAT10 and ADRA2A were upregulated, FOXO1 did not change in the NASH group of patients. The most important finding is that compared with the ASH group of patients, the expression levels of all three molecules were significantly lower than in the NASH group of patients (p < 0.001 in all molecules). These results confirmed our previous finding that there are significant differences of molecules change in ASH compared to NASH. Thus, we conclude that there are significantly different molecules and pathways involved during the pathogenesis of HCC development in ASH compared to NASH which could help explain why the tumorigenic rate is different in ASH and NASH.

Liao CL, Chu YL, Lin HY, et al.
Anticancer Res. 2018; 38(7):3989-3997 [PubMed] Related Publications
BACKGROUND/AIM: Bisdemethoxycurcumin (BDMC) exhibits biological activities including anticancer and anti-metastasis in human cancer cell lines, but there is no available information to show whether BDMC suppresses cell migration and invasion of human cervical cancer cells.
MATERIALS AND METHODS: Wound-healing, migration, invasion, zymography, and western blotting assays were used to investigate the effects of BDMC on HeLa cells in vitro.
RESULTS: BDMC reduced the total viable cell number in a dose-dependent manner. The wound-healing assay show BDMC suppressed the movement of HeLa cells. Furthermore, the trans-well chamber assays showed that BDMC suppressed the cell migration and invasion. Gelatin zymograph assay showed that BDMC did not inhibit matrix metalloproteinase-2 (MMP-2) and -9 activities in vitro. However, western blotting assay showed that BDMC significantly reduced protein levels of growth factor receptor-bound protein 2 (GRB2), Ras homolog gene family, member A (Rho A), urokinase-type plasminogen activator (uPA), RAS, MMP-2, and N-cadherin but increased those of phosphor-extracellular-signal related kinase (p-ERK1/2), E-cadherin and nuclear factor-ĸB (NF-ĸB) in HeLa cells. Confocal laser microscopy assay was used to further confirm BDMC increased NF-ĸB when compared to controls.
CONCLUSION: BDMC may have potential as a novel anti-metastasis agent for the treatment of human cervical cancer.

Morgan MA, Shilatifard A
Epigenetic ConFUSION: SS18-SSX Fusion Rewires BAF Complex to Activate Bivalent Genes in Synovial Sarcoma.
Cancer Cell. 2018; 33(6):951-953 [PubMed] Related Publications
In this issue of Cancer Cell, McBride and colleagues report that the synovial sarcoma SS18-SSX fusion drives BAF complex recruitment to bivalent domains repressed by PRC2 complex to orchestrate aberrant transcriptional activation. Redistribution of BAF localization is a major driver of synovial sarcoma proliferation and presents a promising therapeutic target.

Li J, Xu J, Yan X, et al.
MicroRNA-485 plays tumour-suppressive roles in colorectal cancer by directly targeting GAB2.
Oncol Rep. 2018; 40(1):554-564 [PubMed] Related Publications
Colorectal cancer (CRC) is reported to be the third most common cancer and the fourth leading cause of cancer-related deaths around the world. MicroRNA-485 (miR-485) has been reported to be aberrantly expressed and play important roles in several types of human malignancy. However, the expression level, biological functions and underlying molecular mechanisms of miR-485 in CRC remain unclear. Therefore, the aim of the present study was to determine miR-485 expression levels and their clinical significance in CRC and to explore the functions and underlying mechanisms of miR-485 in this disease. In the present study, miR-485 was lowly expressed in CRC tissues and cell lines. Decreased miR-485 expression was associated with tumour size, lymph node metastasis, distant metastasis and TNM stage. Functional assays indicated that upregulation of miR-485 impaired CRC cell proliferation, invasion and induced cell apoptosis. Grb2-associated binding 2 (GAB2) was identified as a direct target of miR-485 in CRC. GAB2 was upregulated in CRC tissues and was negatively correlated with the miR-485 expression level. Furthermore, GAB2 knockdown simulated the tumour-suppressing roles of miR-485 overexpression in CRC cells. Moreover, restored GAB2 expression reversed the effects of miR-485 overexpression in CRC cells. In addition, miR-485 suppressed the AKT and ERK signalling pathways in CRC by directly targeting GAB2. Collectively, these findings demonstrate that miR-485 may play tumour suppressive roles in CRC by directly targeting GAB2 and indirectly regulating AKT and ERK signalling pathways, suggesting that miR-485 may be a potential therapeutic target for patients with this disease.

Ruiz-Saenz A, Dreyer C, Campbell MR, et al.
HER2 Amplification in Tumors Activates PI3K/Akt Signaling Independent of HER3.
Cancer Res. 2018; 78(13):3645-3658 [PubMed] Related Publications
Current evidence suggests that HER2-driven tumorigenesis requires HER3. This is likely due to the unique ability of HER3 to activate PI3K/Akt pathway signaling, which is not directly accessible to HER2. By genetic elimination of HER3 or shRNA knockdown of HER3 in HER2-amplified cancer cells, we find residual HER2-driven activation of PI3K/Akt pathway signaling that is driven by HER2 through direct and indirect mechanisms. Indirect mechanisms involved second messenger pathways, including Ras or Grb2. Direct binding of HER2 to PI3K occurred through p-Tyr1139, which has a weak affinity for PI3K but becomes significant at very high expression and phosphorylation. Mutation of Y1139 impaired the tumorigenic competency of HER2. Total elimination of HER3 expression in HCC1569 HER2-amplified cancer cells significantly impaired tumorigenicity only transiently, overcome by subsequent increases in HER2 expression and phosphorylation with binding and activation of PI3K. In contrast to activation of oncogenes by mutation, activation by overexpression was quantitative in nature: weak intrinsic activities were strengthened by overexpression, with additional gains observed through further increases in expression. Collectively, these data show that progressive functional gains by HER2 can increase its repertoire of activities such as the activation of PI3K and overcome its dependency on HER3.

Berbegall AP, Bogen D, Pötschger U, et al.
Heterogeneous MYCN amplification in neuroblastoma: a SIOP Europe Neuroblastoma Study.
Br J Cancer. 2018; 118(11):1502-1512 [PubMed] Article available free on PMC after 18/10/2019 Related Publications
BACKGROUND: In neuroblastoma (NB), the most powerful prognostic marker, the MYCN amplification (MNA), occasionally shows intratumoural heterogeneity (ITH), i.e. coexistence of MYCN-amplified and non-MYCN-amplified tumour cell clones, called heterogeneous MNA (hetMNA). Prognostication and therapy allocation are still unsolved issues.
METHODS: The SIOPEN Biology group analysed 99 hetMNA NBs focussing on the prognostic significance of MYCN ITH.
RESULTS: Patients <18 months (18 m) showed a better outcome in all stages as compared to older patients (5-year OS in localised stages: <18 m: 0.95 ± 0.04, >18 m: 0.67 ± 0.14, p = 0.011; metastatic: <18 m: 0.76 ± 0.15, >18 m: 0.28 ± 0.09, p = 0.084). The genomic 'background', but not MNA clone sizes, correlated significantly with relapse frequency and OS. No relapses occurred in cases of only numerical chromosomal aberrations. Infiltrated bone marrows and relapse tumour cells mostly displayed no MNA. However, one stage 4s tumour with segmental chromosomal aberrations showed a homogeneous MNA in the relapse.
CONCLUSIONS: This study provides a rationale for the necessary distinction between heterogeneous and homogeneous MNA. HetMNA tumours have to be evaluated individually, taking age, stage and, most importantly, genomic background into account to avoid unnecessary upgrading of risk/overtreatment, especially in infants, as well as in order to identify tumours prone to developing homogeneous MNA.

Shi Q, Wang Y, Mu Y, et al.
MiR-433-3p Inhibits Proliferation and Invasion of Esophageal Squamous Cell Carcinoma by Targeting GRB2.
Cell Physiol Biochem. 2018; 46(5):2187-2196 [PubMed] Related Publications
BACKGROUND/AIMS: MicroRNAs (miRNAs) are non-coding single stranded RNAs of 17-25 nucleotides in size, and their altered expression has been observed in various cancers. Previous studies have confirmed that miR-433-3p has effects on cancer cell proliferation, invasion, and migration, and its expression also correlates with sensitivity to chemotherapy. However, to date, there have been no studies on the biological functions of miR-433-3p in esophageal squamous cell carcinoma (ESCC).
METHODS: The Cell Counting Kit-8, transwell, and matrigel assays were used to test the effects of miR-433-3p and its predicted target, growth factor receptor-bound protein 2 (GRB2), on the proliferation, migration, and invasion of Eca109 and KYSE30 cells, two types of esophageal cancer cell lines. The miR-433-3p binding site in the 3' untranslated region (UTR) region of GRB2 was predicted and verified using miRNA target site prediction software and structuring correct mutant examination. Western blotting and fluorescent quantitative PCR (FQ-PCR) techniques were employed to evaluate GRB2 expression. The inhibitory effects of miR-433-3p on tumor growth were investigated using a tumor xenograft model.
RESULTS: The binding site of miR-433-3p was identified in the 3'UTR region of GRB2. Western blotting and FQ-PCR showed that miR-433-3p inhibited the mRNA and protein expression of GRB2. Overexpression of GRB2 inhibited tumorigenesis in nude mice. MiR-433-3p overexpression inhibited the proliferation, migration, and invasion of ESCC cells by suppressing GRB2 gene expression.
CONCLUSIONS: Our findings suggest that targeting miR-433-3p may have therapeutic benefits in ESCC.

Lin CC, Kuo CL, Huang YP, et al.
Demethoxycurcumin Suppresses Migration and Invasion of Human Cervical Cancer HeLa Cells
Anticancer Res. 2018; 38(5):2761-2769 [PubMed] Related Publications
BACKGROUND/AIM: Demethoxycurcumin (DMC), one of the curcuminoids present in turmeric, has been shown to induce cell death in many human cancer cell lines, however, there has not been any investigation on whether DMC inhibits metastatic activity in human cervical cancer cells in vitro. In the present study, DMC at 2.5-15 μM decreased cell number, thus, we used IC
MATERIALS AND METHODS: The wound healing, migration, invasion, zymography, and western blotting assays were used to investigate the effects of DMC on HeLa cells.
RESULTS: The wound healing assay was used to show that DMC suppressed cell movement of HeLa cells. Furthermore, the trans-well chamber assay was used to show that DMC suppressed HeLa cell migration and invasion. Gelatin zymography assay did not show any significant effects of DMC on the gelatinolytic activity (MMP-2 and -9) in conditioned media of HeLa cells treated by DMC. Western blotting showed that DMC significantly reduced protein levels of GRB2, MMP-2, ERK1/2, N-cadherin and Ras but increased the levels of E-cadherin and NF-κB in HeLa cells. Confocal laser microscopy indicated that DMC increased NF-κB in HeLa cells confirming the results from Western blotting.
CONCLUSION: DMC may be used as a novel anti-metastatic agent for the treatment of human cervical cancer in the future.

Jiang H, Dong L, Gong F, et al.
Inflammatory genes are novel prognostic biomarkers for colorectal cancer.
Int J Mol Med. 2018; 42(1):368-380 [PubMed] Article available free on PMC after 18/10/2019 Related Publications
Inflammatory genes serve a crucial role in the pathogenesis of inflammation‑associated tumors. However, as recent studies have mainly focused on the effects of single inflammatory genes on colorectal cancer (CRC), but not on the global interactions between genes, the underlying mechanisms between inflammatory genes and CRC remain unclear. In the current study, two inflammation‑associated networks were constructed based on inflammatory genes, differentially expressed genes (DEGs) in CRC vs. normal samples, and protein‑protein interactions (PPIs). These networks included an inflammation‑related neighbor network (IRNN) and an inflammation‑related DEG network (IRDN). Notably, the results indicated that the inflammatory genes served as important CRC‑associated genes in the IRNN. Certain inflammatory genes were more likely to be network hubs and exhibited higher betweenness centralities, indicating that these inflammatory hub genes had central roles in the communication between genes in the IRNN. By contrast, in the IRDN, functional enrichment analysis revealed that genes were enriched in numerous cancer‑associated functions and pathways. Subsequently, 14 genes in a module were identified in the IRDN as the potential biomarkers associated with disease‑free survival (DFS) in CRC patients in the GSE24550 dataset, the prognosis of which was further validated using three independent datasets (GSE24549, GSE34551 and GSE103479). All 14 genes (including BCAR1, CRK, FYN, GRB2, LCP2, PIK3R1, PLCG1, PTK2, PTPN11, PTPN6, SHC1, SOS1, SRC and SYK) in this module were inflammatory genes, emphasizing the critical role of inflammation in CRC. In conclusion, these findings based on integrated inflammation‑associated networks provided a novel insight that may help elucidate the inflammation‑mediated mechanisms involved in CRC.

McManus S, Chababi W, Arsenault D, et al.
Dissecting Oncogenic RTK Pathways in Colorectal Cancer Initiation and Progression.
Methods Mol Biol. 2018; 1765:27-42 [PubMed] Related Publications
Colorectal cancer (CRC) is a progressive disorder associated with an accumulation of multiple heterogeneous genetic alterations in intestinal epithelial cells (IEC). However, when these cells undergo neoplastic transformation and become cancerous and metastatic, they invariably acquire hallmarks conferring them the ability to hyperproliferate, escape growth-inhibitory and death-inducing cues, and promote angiogenesis as well as epithelial-to-mesenchymal transformation (EMT), fostering their invasive dissemination from primary tumor into distant tissues. Compelling clinical and experimental evidence suggest that aberrant engagement of cell surface growth factor receptor tyrosine kinase (RTK) signaling, like that of the hepatocyte growth factor (HGF)/MET receptor, underlies CRC metastatic progression by promoting these cancer hallmarks. To date, though, the use of RTK-targeting agents has been viewed as a promising approach for the treatment of metastatic CRC, clinical success has been modest.Our vision is that the prospect of designing RTK-based, improved and innovative CRC therapies and prognostic markers likely rests on a comprehensive understanding of the biological processes and underlying regulatory molecular mechanisms by which deregulation of RTK signaling governs IEC's neoplastic transformation and their transition from noninvasive to metastatic and malignant cells. Herein, we describe our scheme for defining the full scope of oncogenic MET-driven cancer biological processes, in cellulo and in vivo, as well as the individual contribution of MET-binding effectors in a nontransformed IEC model, the IEC-6 cell line.

Herr R, Halbach S, Heizmann M, et al.
BRAF inhibition upregulates a variety of receptor tyrosine kinases and their downstream effector Gab2 in colorectal cancer cell lines.
Oncogene. 2018; 37(12):1576-1593 [PubMed] Related Publications
BRAF mutations occur in ~10% of colorectal cancer (CRC) and are associated with poor prognosis. Inhibitors selective for the BRAF

Nakagawa Y, Ashihara E, Yao H, et al.
Multiple myeloma cells adapted to long-exposure of hypoxia exhibit stem cell characters with TGF-β/Smad pathway activation.
Biochem Biophys Res Commun. 2018; 496(2):490-496 [PubMed] Related Publications
The emergence of new molecular targeting agents has improved the prognosis of patients with multiple myeloma (MM). However, MM remains incurable because MM stem cells are likely resistant to these agents. Thus, it is important to further investigate the biology of MM stem cells, which reside in the hypoxic bone marrow niche. In this study, we established and investigated the characteristics of hypoxia-adapted MM (HA-MM) cells, which could proliferate for more than six months under hypoxic conditions (1% O

Nguyen L, Masouminia M, Mendoza A, et al.
Alcoholic hepatitis versus non-alcoholic steatohepatitis: Levels of expression of some proteins involved in tumorigenesis.
Exp Mol Pathol. 2018; 104(1):45-49 [PubMed] Article available free on PMC after 18/10/2019 Related Publications
Non-alcoholic steatohepatitis (NASH) is commonly associated with obesity, type 2 diabetes, and/or hypertriglyceridemia, while alcoholic steatohepatitis (ASH) is associated with alcohol abuse. Both NASH and ASH patients can develop cirrhosis and hepatocellular carcinoma (HCC) if left untreated. However, the rate of tumorigenesis in NASH and ASH appears to be different. Individuals with NASH progress to HCC at a rate of 0.5% annually (Lindenmeyer and McCullough, 2018), when individuals with ASH progress to HCC at a rate of 3-10% annually (Schwartz and Reinus, 2012). Thus, the objective of our study is to determine if there are differences in NASH versus ASH in the levels of different proteins expressed involved in cancer development. The method used was measuring the proteins expressed in liver biopsied sections from NASH and ASH patients using immunohistochemical staining with fluorescent antibodies and then quantitating the fluorescence intensity morphometrically. The 20 proteins tested are parts of the Ingenuity Canonical Pathway of Molecular Mechanisms of Cancer and include: RAP2B, NAIP, FYN, PAK6, SUV39H1, GNAI1, BAX, E2F3, CKDN2B, BAK1, BCL2, DIABLO, RASGRF2, GNA15, PIK3CB, BRCA1, MAP2K1, BIRC3, CDK2, and ATM. In ASH, the proteins that showed upregulated levels of expression were SUV39H1, E2F3, BCL2, BAK1, BIRC3, and GNAI1. In NASH, the proteins that showed upregulated levels of expression were BAK1 and GNAI1 and the protein that showed downregulated level of expression was BCL2. Additionally, levels of expression for SUV39H1, E2F3, BCL2, BAK1, BIRC3, and GNAI1 were significant upregulated in ASH compared to NASH. These results showed significant differences in ASH compared to normal liver, and significant differences in ASH compared to NASH. Thus, we conclude that there are more proteins involved in tumorigenesis in ASH compared to NASH and in ASH compared to normal liver, which is consistent with the known tumor development rate in ASH and NASH.

Ijaz M, Wang F, Shahbaz M, et al.
The Role of Grb2 in Cancer and Peptides as Grb2 Antagonists.
Protein Pept Lett. 2018; 24(12):1084-1095 [PubMed] Related Publications
BACKGROUND: Growth factor receptor-bound protein 2 (Grb2) is a 25 kDa adaptor protein, which was originally discovered to accomplish basic cellular events such as cell growth, cell proliferation, and metabolism. However, recent studies evidenced that Grb2 was largely involved in multiple tumor malignancies. The mature Grb2 is a 217 amino acid sequence, which consists of one Src homology 2 (SH2) domain flanked by two Src homology 3 (SH3) domains. Using these binding motives, the ubiquitously expressed Grb2 acts as an intermediate between cell-surface activated receptors and downstream targets.
OBJECTIVES: Consequently, the Grb2 becomes the key element of this oncogenesis and launched a number of defected signaling cascades. Therefore, vast concern of the Grb2 in multiple cancer patterns makes it an attractive therapeutic target. In this review, we have compiled the maximum tumor conformations caused by the involvement of the Grb2, the central role of Grb2 in numerous oncogenic pathways and particular approaches that can be useful to downregulate the Grb2 overexpression. We will discuss in details the activity of different types of novel peptides, their high affinity for the Grb2 protein and blockade of Grb2 mediated signaling pathways by targeting the SH2/SH3 binding sites.
METHODS & RESULTS: There is a three-fold aspect to this review: Grb2 protein introduction, Grb2 protein involvement in cancer, and the role of peptides as Grb2 antagonists. First, Grb2 and compiled maximum tumor conformations induced by Grb2 involvement were introduced. Secondly, several oncogenic pathways of Grb2 involvement and particular approaches potentially useful to downregulate Grb2 overexpression were outlined. The activity of different types of novel peptides for the Grb2 protein was also detailed. Last but not least, the blockade of Grb2-mediated signaling pathways by targeting SH2/SH3 binding sites were summarized.
CONCLUSION: We have epitomized the utmost cancer malignancies caused by abnormal signaling of the Grb2 adaptor molecule. Indeed, Grb2's enormous involvement in the progression and development of different cancers broaden our tactics to build anticancer drug candidates. Depending on the high affinity and increased specificity we have described the major potent peptides which may efficiently target and block the SH2 or SH3 arms of the Grb2. It may be of benefit for developing novel anticancer peptides. However, further work is needed to pinpoint more binding motives of Grb2 to generate efficacious anticancer agents for diverse human cancers in the near future.

Naidu S, Shi L, Magee P, et al.
PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways.
Sci Rep. 2017; 7(1):15441 [PubMed] Article available free on PMC after 18/10/2019 Related Publications
In NSCLC alterations in PDGF receptors are markers of worst prognosis and efficient targeting of these receptors is yet to be achieved. In this study, we explored PDGFR-regulated microRNAs demonstrating that miR-23b cluster and miR-125a-5p are downregulated by increased expression of PDGFR-α or PDGFR-β in NSCLC cells. Mechanistically, the expression of these microRNAs is positively regulated by p53 and negatively modulated by NF-kB p65. Forced expression of miR-23b cluster or miR-125a-5p enhanced drug sensitivity and suppressed invasiveness of NSCLC cells by silencing several genes involved in oncogenic KRAS and NF-kB pathways, including SOS1, GRB2, IQGAP1, RALA, RAF-1, IKKβ, AKT2, ERK2 and KRAS itself. Of note, an inverse correlation between miR-23b cluster, miR-125a-5p and respective target genes was also found in vivo in a large dataset of lung adenocarcinoma samples. Furthermore, in vivo delivery of miR-23b cluster or miR-125a-5p significantly repressed tumour growth in a highly aggressive NSCLC circulating tumour cell (CTC) patient derived explant (CDX) mouse model. In conclusion, our finding sheds light on the PDGFR signaling and endorses the possibility to employ miR-23b cluster and miR-125a-5p as therapeutic tools to silence simultaneously a range of redundant pathways and main effectors of tumorigenesis in NSCLC.

Adachi Y, Watanabe K, Kita K, et al.
Resistance mediated by alternative receptor tyrosine kinases in FGFR1-amplified lung cancer.
Carcinogenesis. 2017; 38(11):1063-1072 [PubMed] Related Publications
Fibroblast growth factor receptor 1 (FGFR1) amplification has been identified in 10-20% of patients with squamous non-small-cell lung cancer. Preclinical models showed promising activity of specific FGFR inhibitors, but early clinical trials showed that only a small fraction of patients with FGFR1-amplified lung cancer responded to FGFR inhibitors. These unsatisfactory results were partly explained by heterogeneous amplicons around the 8p11 genomic region, leading to false-positive amplification results. Furthermore, discrepancies in the gene amplification and protein expression of FGFR1 were also reported. In this study, we identified the roles of alternative receptor tyrosine kinases (RTKs) in FGFR1-amplified lung cancer. These alternative RTKs dominantly activate phosphoinositide 3-kinase-AKT signaling and also mitigate sustained inhibition of mitogen-activated protein kinase signaling by FGFR inhibitors. The rebound activation of extracellular signal-regulated kinase phosphorylation was associated with sensitivity to the drugs. Combinatorial inhibition of alternative RTKs and FGFR1 was required to suppress both AKT and extracellular signal-regulated kinase phosphorylation and to induce key pro-apoptotic proteins BIM and p53 upregulated modulator of apoptosis (PUMA). Furthermore, even in FGFR inhibitor-sensitive NCI-H1581 lung cancer cells, MET-expressing clones were already detectable at a very low frequency before resistance induction. Selection of these pre-existing subclones resulted in FGFR inhibitor resistance because of the activation of AKT and extracellular signal-regulated kinase by MET signaling that was mediated by GRB2 associated binding protein 1 (GAB1). These results suggest that incomplete suppression of key survival signals led to intrinsic and acquired resistance to FGFR inhibitors. Our results may help explain the low clinical response rates to FGFR inhibitors in FGFR1-amplified lung cancer.

Lin X, Gu Y, Kapoor A, et al.
Overexpression of MUC1 and Genomic Alterations in Its Network Associate with Prostate Cancer Progression.
Neoplasia. 2017; 19(11):857-867 [PubMed] Article available free on PMC after 18/10/2019 Related Publications
We investigate the association of MUC1 with castration-resistant prostate cancer (CRPC), bone metastasis, and PC recurrence. MUC1 expression was studied in patient-derived bone metastasis and CRPCs produced by prostate-specific PTEN

Xu L, Li J, Kuang Z, et al.
Knockdown of Gab1 Inhibits Cellular Proliferation, Migration, and Invasion in Human Oral Squamous Carcinoma Cells.
Oncol Res. 2018; 26(4):617-624 [PubMed] Related Publications
Grb2-associated binder 1 (Gab1) is often aberrant in cancerous cells and tissues, whose alteration is responsible for aggressive phenotypes. In this study, we examined the Gab1 expression in human oral squamous cell carcinoma (OSCC) tissues and investigated the cellular and molecular effect of Gab1 on migration, invasion, and cell growth of the OSCC cell lines SCC15 and SCC25. We found that Gab1 was overexpressed in OSCC tissues and cells, which is related to the protein levels of various molecules associated with cellular proliferation, migration, and invasion. Functional assays identified that Gab1 overexpression promoted cell proliferation and invasion of OSCC cells and inhibited cell apoptosis in the SCC15 and SCC25 cell lines. On the other hand, Gab1 silencing affected the proliferation and invasion of OSCC cells and induced cell apoptosis. Western blot assay identified that Gab1 overexpression suppressed the expression of Cdc20 homolog 1 (Cdh1) and then promoted cell invasion in OSCC cells. Furthermore, Gab1-mediated Cdh1 downregulation was significantly reversed when the cells were subjected to an inhibitor of p-Akt. In conclusion, these results suggested that Gab1 induced malignant progression of OSCC cells probably via activation of the Akt/Cdh1 signaling pathway. Thus, Gab1 may be a potential therapeutic target in the treatment of OSCC patients.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. GRB2, Cancer Genetics Web: Accessed:

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 30 August, 2019     Cancer Genetics Web, Established 1999