Gene Summary

Gene:SATB1; SATB homeobox 1
Summary:This gene encodes a matrix protein which binds nuclear matrix and scaffold-associating DNAs through a unique nuclear architecture. The protein recruits chromatin-remodeling factors in order to regulate chromatin structure and gene expression. [provided by RefSeq, Apr 2016]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:DNA-binding protein SATB1
Source:NCBIAccessed: 01 September, 2019


What does this gene/protein do?
Show (24)

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 01 September 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.

  • Liver Cancer
  • Apoptosis
  • Gene Expression Profiling
  • Epithelial-Mesenchymal Transition
  • Jurkat Cells
  • Staging
  • Chromatin
  • Matrix Attachment Region Binding Proteins
  • Cell Movement
  • DNA-Binding Proteins
  • beta Catenin
  • Carcinogenesis
  • siRNA
  • Multivariate Analysis
  • Gene Knockdown Techniques
  • Immunohistochemistry
  • Colorectal Cancer
  • Down-Regulation
  • Neoplasm Metastasis
  • Promoter Regions
  • Biomarkers, Tumor
  • Cancer Gene Expression Regulation
  • DNA Methylation
  • MicroRNAs
  • Cell Proliferation
  • Lymphatic Metastasis
  • Gene Expression
  • Neoplastic Cell Transformation
  • Chromosome 3
  • Lung Cancer
  • Western Blotting
  • Tumor Escape
  • Messenger RNA
  • Hepatocellular Carcinoma
  • Stomach Cancer
  • Follow-Up Studies
  • Neoplasm Invasiveness
  • Epigenetics
  • Proportional Hazards Models
  • Disease Progression
  • Breast Cancer
Tag cloud generated 01 September, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (5)

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: SATB1 (cancer-related)

Cao C, Wang Q, Li Q, et al.
Development and Preliminary Clinical Application of Circulating Tumor Cell Detection System for Prostate Cancer.
J Biomed Nanotechnol. 2019; 15(3):612-620 [PubMed] Related Publications
Real-time detection of circulating tumor cell (CTC) markers that are constantly changing and renewing during disease progression is of great significance for the timely regimen switch or individualized target therapy. The abnormally expressed special AT-rich sequence binding protein 1 (SATB1), a nuclear matrix attachment region binding protein, in various tumors, promotes the growth and metastasis of tumor cells by regulating gene expression. In this paper, a CTC detection system for prostate cancer (PCa) was developed on the basis of epithelial cell adhesion molecule (EpCAM)-targeted immunomagnetic separation and CK-FITC and SATB-1-APC immunofluorescence assay, and the recovery rate of tumor cells in PBS and simulated whole blood by this system was detected. Subsequently, we isolated, identified, and counted SATB-1 ositive CTCs in the peripheral blood and urine samples of 60 tumor-bearing nude mice, 5 healthy volunteers and 13 PCa patients. Combined with the clinicopathological factors, the clinical value of the system was analyzed, and the possibility of SATB-1-positive CTCs in the diagnosis of PCa was evaluated. The results showed that the CTC sorting and identification system for prostate cancer constructed in this study had a recovery rate of more than 85% for CTC in PBS, urine and blood simulation samples. The expression level of SATB-1 was different in different PCa cell lines, which was relatively high in the highly invasive PCa DU-145 cell line. The expression of SATB-1 in CTCs in the blood samples of PCa patients with different clinical characteristics and in the urine samples of a few PCa patients with bone metastases were different, and the detection sensitivity of peripheral blood was higher than that of urine. This study has important clinical reference value for the early diagnosis of PCa and the evaluation of bone metastasis based on the CTC counting and the SATB-1 expression in CTCs.

Xu HY, Xue JX, Gao H, et al.
Fluvastatin-mediated down-regulation of SATB1 affects aggressive phenotypes of human non-small-cell lung cancer cell line H292.
Life Sci. 2019; 222:212-220 [PubMed] Related Publications
AIMS: Fluvastatin reduces tumor proliferation and increased apoptotic activity in various cancers. Special AT-rich sequence binding protein 1 (SATB1) is a genome organizer that reprogrammes the gene transcription profiles of tumors to promote growth and metastasis. The antitumor effect and molecular mechanisms of fluvastatin on lung cancer is poorly understood. This study aimed to investigate the antitumor effect of fluvastatin on lung cancer and its possible mechanics.
MAIN METHODS: Cell viability assay was used to examine the inhibition of fluvastatin on proliferation of H292 cells. In order to investigate the antitumor mechanics, SATB1 knock-down H292 cells was constructed by lentiviral transfection. RT-PCR and Western blot were performed to examine the effects of fluvastatin on expression of SATB1 and Wnt/β-catenin signaling components.
KEY FINDINGS: Fluvastatin significantly inhibited proliferation and invasion of H292 cells in a time- and dose-dependent manner and promoted the apoptosis (p < 0.05). The expression of SATB1 was down-regulated by fluvastatin in a dose-dependent manner. The proliferation and invasion of SATB1-shRNA cells was significantly suppressed, and the apoptosis was significantly enhanced (p < 0.05). We also show that the common target genes were regulated by SATB1 and Wnt/β-catenin pathway simultaneously. There may be a functional link between SATB1 and Wnt/β-catenin pathway.
SIGNIFICANCE: We presented a possible mechanism of statins that fluvastatin significantly suppressed the in vitro tumor progression of H292 cells possibly by down-regulation of SATB1 via Wnt/β-catenin pathway, which provided new therapeutic possibilities for more cancers driven by hyperexpression of SATB1 and Wnt/β-catenin pathway.

Xu C, Guo H, Kong D, et al.
Ganodermanontriol inhibits expression of special AT rich sequence binding protein 1 gene in human hepatocellular carcinoma.
J Cancer Res Ther. 2018; 14(Supplement):S964-S968 [PubMed] Related Publications
Context: The metastasis of liver cancer is a major cause of clinical treatment failure, restrain, and control the cancer metastasis is the major strategy of the treatment and prevention of the disease. Special AT-rich sequence-binding protein 1 (SATB1) gene was overexpressed in many malignant tumors and considered as a potential target of anticancer drug. This study investigated the mechanism how ganodermanontriol effect the expression of SATB1 and thus inhibits the growth and metastasis in hepatocellular carcinoma (HCC).
Aims: This study explored mainly on the mechanism how ganodermanontriol affects the expression of SATB1 and inhibits proliferation of tumor on human hepatoma cell line HepG2.
Settings and Design: The cancer cells were treated with ganodermanontriol. The status of the cells was detected by different methods. The mechanism was checked by various methods.
Materials and Methods: In HepG2 cancer cells treated with various concentrations of ganodermanontriol, the cell proliferation of was detected by MTT assay, cell apoptosis was analyzed by flow cytometry; the mRNA of SATB1, Bcl-2, Bax were detected by reverse transcription-polymerase chain reaction (RT-PCR) and the protein level of SATB1, Bcl-2, Bax, and caspase 3 were analyzed by Western blot.
Statistical Analysis Used: Data are presented as the mean ± standard deviation. The data were analyzed using SPSS 18.0 software (SPSS, Inc., Chicago, IL, USA) and GraphPad Prism software (GraphPad Software, Inc., La Jolla, CA, USA). A one-way analysis of variance test was used to compare the differences among groups.
Results: This study showed that ganodermanontriol could significantly reduce the expression level of SATB1.
Conclusion: Therefore, downregulate the cascade effect caused by the expression level of Bcl-2 in HCC HepG2 cells.

Naik R, Galande S
SATB family chromatin organizers as master regulators of tumor progression.
Oncogene. 2019; 38(12):1989-2004 [PubMed] Related Publications
SATB (Special AT-rich binding protein) family proteins have emerged as key regulators that integrate higher-order chromatin organization with the regulation of gene expression. Studies over the past decade have elucidated the specific roles of SATB1 and SATB2, two closely related members of this family, in cancer progression. SATB family chromatin organizers play diverse and important roles in regulating the dynamic equilibrium of apoptosis, cell invasion, metastasis, proliferation, angiogenesis, and immune modulation. This review highlights cellular and molecular events governed by SATB1 influencing the structural organization of chromatin and interacting with several co-activators and co-repressors of transcription towards tumor progression. SATB1 expression across tumor cell types generates cellular and molecular heterogeneity culminating in tumor relapse and metastasis. SATB1 exhibits dynamic expression within intratumoral cell types regulated by the tumor microenvironment, which culminates towards tumor progression. Recent studies suggested that cell-specific expression of SATB1 across tumor recruited dendritic cells (DC), cytotoxic T lymphocytes (CTL), T regulatory cells (Tregs) and tumor epithelial cells along with tumor microenvironment act as primary determinants of tumor progression and tumor inflammation. In contrast, SATB2 is differentially expressed in an array of cancer types and is involved in tumorigenesis. Survival analysis for patients across an array of cancer types correlated with expression of SATB family chromatin organizers suggested tissue-specific expression of SATB1 and SATB2 contributing to disease prognosis. In this context, it is pertinent to understand molecular players, cellular pathways, genetic and epigenetic mechanisms governed by cell types within tumors regulated by SATB proteins. We propose that patient survival analysis based on the expression profile of SATB chromatin organizers would facilitate their unequivocal establishment as prognostic markers and therapeutic targets for cancer therapy.

Yang D, Li R, Xia J, et al.
miR‑3666 suppresses cellular proliferation and invasion in colorectal cancer by targeting SATB2.
Mol Med Rep. 2018; 18(6):4847-4854 [PubMed] Free Access to Full Article Related Publications
MicroRNA‑3666 (miR‑3666) acts as a tumor suppressor in cervical cancer, non‑small cell lung cancer and thyroid carcinoma; however, the function of miR‑3666 in colorectal cancer (CRC) remains largely unknown. In the present study, was demonstrated that miR‑3666 was significantly downregulated in CRC tissues compared with in adjacent normal tissues by reverse transcription‑quantitative polymerase chain reaction. Additionally, miR‑3666 may serve as a prognostic biomarker for patients with CRC. Via functional experiments, the present study reported that miR‑3666 overexpression significantly inhibited the proliferation, migration and invasion of CRC cells as determined by Cell Counting Kit‑8 and Transwell assays, and vice versa. In addition, miR‑3666 was reported to directly target special AT‑rich sequence binding protein 2 (SATB2) in CRC cells; overexpression of miR‑3666 significantly suppressed the expression of SATB2 in CRC cells as determined by western blotting. Furthermore, an inverse correlation was observed between the expression levels of miR‑3666 and SATB2 in CRC tissues. Restoration of SATB1 expression significantly reversed the effects of miR‑3666 mimic on CRC cells. In summary, the results of the present study indicated that miR‑3666 may serve as a tumor suppressor in CRC by targeting SATB2.

Liu J, Li Y, Lu Z, et al.
Deceleration of glycometabolism impedes IgG-producing B-cell-mediated tumor elimination by targeting SATB1.
Immunology. 2019; 156(1):56-68 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
B lymphocytes, known as antibody producers, mediate tumor cell destruction in the manner of antibody-dependent cell-mediated cytotoxicity; however, their anti-tumor function seems to be weakened during tumorigenesis, while the underlying mechanisms remain unclear. In this study, we found that IgG mediated anti-tumor effects, but IgG-producing B cells decreased in various tumors. Considering the underlying mechanism, glycometabolism was noteworthy. We found that tumor-infiltrating B cells were glucose-starved and accompanied by a deceleration of glycometabolism. Both inhibition of glycometabolism and deprivation of glucose through tumor cells, or glucose-free treatment, reduced the differentiation of B cells into IgG-producing cells. In this process, special AT-rich sequence-binding protein-1 (SATB1) was significantly silenced in B cells. Down-regulating SATB1 by inhibiting glycometabolism or RNA interference reduced the binding of signal transducer and activator of transcription 6 (STAT6) to the promoter of germline Cγ gene, subsequently resulting in fewer B cells producing IgG. Our findings provide the first evidence that glycometabolic inhibition by tumorigenesis suppresses differentiation of B cells into IgG-producing cells, and altering glycometabolism may be promising in improving the anti-tumor effect of B cells.

Dong J, Cao Y, Shen H, et al.
EGFR aptamer-conjugated liposome-polycation-DNA complex for targeted delivery of SATB1 small interfering RNA to choriocarcinoma cells.
Biomed Pharmacother. 2018; 107:849-859 [PubMed] Related Publications
Choriocarcinoma is a highly aggressive and vascular cancer. The main treatment for choriocarcinoma is the chemotherapy associated with severe side effects. Therefore, the development of novel strategies to eliminate choriocarcinoma is crucial for increasing the health of women. SATB1 (special AT-rich sequence binding protein 1) participates in tissue-specific gene expression and higher-order chromatin organization, and could promote cancer progression and invasion. For the first time, we hereby demonstrated that the expression of SATB1 was increased by 19 folds in choriocarcinoma cells compared with the normal chorionic cell line, and inhibition of SATB1 expression could markedly inhibit the proliferation of choriocarcinoma cells. Then we developed the gene drug delivery system EGFR-LPDS (epidermal growth factor receptor aptamer-conjugated liposome-polycation-DNA complex loaded with SATB1 siRNA) to increase the delivery and therapeutic effect of SATB1 siRNA against choriocarcinoma cells. The results showed that EGFR-LPDS could specifically target choriocarcinoma cells, resulting in significant inhibition of SATB1 expression, growth inhibitory effect and apoptosis in EGFR over-expressing choriocarcinoma cells in vitro. Notably, EGFR-LPDS could inhibit the expression of SATB1 in choriocarcinoma xenograft in mice, and exhibited the best therapeutic efficacy against mice bearing choriocarcinoma xenograft compared with other controls. Notably, EGFR-LPDS achieved a striking tumor weight inhibitory rate of 81.4%. This is the first report of the therapeutic efficacy of SATB1 siRNA towards choriocarcinoma, and the increased SATB1 siRNA delivery by nanoparticles to choriocarcinoma cells using EGFR aptamers. Thus, EGFR-LPDS represents an up-and coming approach for choriocarcinoma therapy. Considering that there are still limited treatment strategies for choriocarcinoma therapy, patients with choriocarcinoma may be beneficial from this gene therapy.

Yang B, Ma YB, Chu SH
Silencing SATB1 overcomes temozolomide resistance by downregulating MGMT expression and upregulating SLC22A18 expression in human glioblastoma cells.
Cancer Gene Ther. 2018; 25(11-12):309-316 [PubMed] Related Publications
Glioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system and has a very poor prognosis. Currently, patients were treated by resection followed by radiotherapy plus concurrent temozolomide (TMZ) chemotherapy. However, many patients are resistant to TMZ-induced DNA damage because of upregulated expression of the DNA repair enzyme O

Xiang J, Zhou L, Zhuang Y, et al.
Lactate dehydrogenase is correlated with clinical stage and grade and is downregulated by si‑SAΤB1 in ovarian cancer.
Oncol Rep. 2018; 40(5):2788-2797 [PubMed] Related Publications
Lactate, which is regulated by gene expression, is largely believed to favor tumor growth and survival. Elevated lactate dehydrogenase (LDH) is a negative prognostic biomarker because it is a key enzyme involved in cancer metabolism. Our previous study revealed that special AT‑rich‑binding protein 1 (SATB1), a genome‑organizing protein, was strongly associated with high metastasis rates in ovarian cancer. However, its underlying molecular mechanisms in ovarian cancer are unclear. In the present study, we investigated whether SATB1 modulated LDH expression and examined the relationship between SATB1 and LDH in ovarian cancer. We employed transient siRNA‑mediated knockdown of SATB1 in ovarian cancer and explored the effects of this knockdown on the expression levels of key glucose metabolism‑related enzyme genes (G6PD, LDH, MDH1, PFK1 and TGM1) and the glucose metabolism‑related protein monocarboxylate transporter 1 (MCT1). We comprehensively analyzed the cellular and molecular role of LDH in ovarian cancer to determine whether it could be a conventional clinicopathological parameter. SATB1 knockdown significantly downregulated both LDH and MCT1 levels and markedly upregulated BRCA1 and BRCA2 levels in ovarian cancer cells (P<0.05). Serum LDH levels in ovarian cancer patients were significantly higher than those in patients with benign ovarian tumors (P<0.05). LDH levels at different stages and grades differed significantly in ovarian cancer. Survival curves revealed that higher LDH expression was correlated with shorter survival (P<0.05). SATB1 may reprogram energy metabolism in ovarian cancer by regulating LDH and MCT1 levels to promote metastasis. Serum LDH levels presented diagnostic accuracy with high specificity and may have potential as a conventional clinicopathological parameter for ovarian cancer.

Zhou G, Jiang H, Ma L
MicroRNA‑376a inhibits cell proliferation and invasion in osteosarcoma via directly targeting SATB1.
Mol Med Rep. 2018; 18(3):3521-3528 [PubMed] Related Publications
Aberrantly expressed microRNAs (miRs) are implicated in the regulation of osteosarcoma (OS) onset and development. Therefore, key miRs in OS must be identified to develop promising and effective therapeutic targets for patients with OS. In the present study, reverse transcription‑quantitative polymerase chain reaction analysis revealed that miR‑376a‑3p expression was downregulated in OS tissues and cell lines. Additionally, decreased miR‑376a expression was associated with tumor size and lymph node infiltration. Restoration of miR‑376a expression reduced cell proliferation and invasion of OS. Furthermore, special AT‑rich sequence‑binding protein 1 (SATB1) was identified as a direct target gene of miR‑376a in OS cells. Furthermore, SATB1 was overexpressed in OS tissues and SATB1 overexpression was inversely correlated with the expression level of miR‑376a. In addition, ectopic SATB1 expression counteracted the inhibitory effects of miR‑376a overexpression on the proliferation and invasion of OS cells. All these results identified that reduced miR‑376a expression may be implicated in the mechanism underlying OS progression, suggesting that the miR‑376a/SATB1 axis may be a promising novel target for potential therapeutic methods for the effective treatment of patients with OS.

Kobierzycki C, Grzegrzolka J, Glatzel-Plucinska N, et al.
Expression of p16 and SATB1 in Invasive Ductal Breast Cancer - A Preliminary Study.
In Vivo. 2018 Jul-Aug; 32(4):731-736 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
BACKGROUND/AIM: An impaired cell-cycle control and genetic material organization are crucial elements of carcinogenesis. p16 is a tumor suppressor protein which decelerates promotion of the cells from G
MATERIALS AND METHODS: The study was performed on 130 samples of archived invasive ductal breast cancers. Immunohistochemical reactions were performed on freshly prepared tissue microarrays and subsequently scanned by a histologic scanner. Reactions were evaluated separately in the cytoplasm (p16c, SATB1c) and nucleus (p16n, SATB1n, Ki-67) with use of a quantification software under researcher supervision.
RESULTS: Expression was observed for Ki-67 in 100%, p16c in 90%, p16n in 89.2%, SATB1c in 98.5% and SATB1n in 87.7% of cancer cases. Statistical analysis showed strong positive correlations: p16c vs. p16n and SATB1c vs. SATB1n (p<0.001 for both) and weak positive correlations: p16c vs. SATB1c and p16c vs. SATB1n (p=0.008, p=0.027; respectively). Expression of p16n was stronger in G
CONCLUSION: A weak association between immunohistochemical expression of p16 and SATB1 indicated limited possibility of their independent usage. Further studies concerning determination of a wider panel of proteins controlling cell cycle should be considered.

Sunkara KP, Gupta G, Hansbro PM, et al.
Functional relevance of SATB1 in immune regulation and tumorigenesis.
Biomed Pharmacother. 2018; 104:87-93 [PubMed] Related Publications
The Special AT-rich Sequence Binding Protein 1 (SATB1) is a chromatin organiser and transcription factor which regulates numerous cellular processes such as differentiation, proliferation and apoptosis through effects on gene expression. SATB1 undergoes various post-translational modifications, which determine its interaction with co-activators and co-repressors to induce regulation of gene transcription. SATB1 is an identified oncogene, its increased expression is associated with poor prognosis in many cancers. This paper provides a review on SATB1-mediated immune responses and on its target genes in the context of tumorigenesis and tumour progression. Specifically, we discuss the role of SATB1 in tumour immunity, Epithelial to Mesenchymal Transition (EMT), metastasis and multidrug resistance. Therapeutic targeting of aberrant SATB1 may be an important strategy in the treatment of cancer.

Fredholm S, Willerslev-Olsen A, Met Ö, et al.
SATB1 in Malignant T Cells.
J Invest Dermatol. 2018; 138(8):1805-1815 [PubMed] Related Publications
Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32), whereas increased SATB1 expression had the opposite effect, indicating that the microRNA-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5 and its upstream activator JAK3 triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic JAK3/STAT5/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis.

Sun J, Yi S, Qiu L, et al.
SATB1 Defines a Subtype of Cutaneous CD30
J Invest Dermatol. 2018; 138(8):1795-1804 [PubMed] Related Publications
Cutaneous CD30

Ding M, Pan J, Guo Z, et al.
SATB1 is a Novel Molecular Target for Cancer Therapy.
Cancer Invest. 2018; 36(1):28-36 [PubMed] Related Publications
The special AT-rich sequence binding-protein1 (SATB1) attracts excessive attention due to its high expression in a variety of malignancies. SATB1 reprograms chromatin and transcription profiles to promote tumor cell growth and invasion and inhibit apoptosis, leading to tumor progression and metastasis. Consistently, silencing SATB1 with small interfering RNA inhibits the growth and invasion of some kinds of tumors. In this review, we highlight recent progress in our understanding of the role of SATB1 as global regulator of gene expression during cancer development, and evaluate the potential of SATB1 as a molecular therapeutic target for cancers with aberrant SATB1 expression.

Glatzel-Plucinska N, Piotrowska A, Grzegrzolka J, et al.
SATB1 Level Correlates with Ki-67 Expression and Is a Positive Prognostic Factor in Non-small Cell Lung Carcinoma.
Anticancer Res. 2018; 38(2):723-736 [PubMed] Related Publications
BACKGROUND: Non-small cell lung carcinomas (NSCLCs), mainly adenocarcinoma (AC) and squamous cell carcinoma (LSCC), account for about 80% of all lung cancer cases. One of the proteins involved in NSCLC progression may be special AT-rich binding protein 1 (SATB1), a potent transcriptional regulator, able to control the expression of whole sets of genes simultaneously. SATB1 has been found to be associated with aggressive phenotype and poor prognosis in numerous malignancies, including breast, colon, ovary and prostate cancer. However, its role in NSCLC is still not fully understood. The aim of this study was to investigate the expression of SATB1 protein and mRNA in NSCLC and non-malignant lung tissue (NMLT) samples, as well as to determine possible relationships of SATB1 expression with both the expression of Ki-67 and the clinicopathological data of the patients.
MATERIALS AND METHODS: The study was performed on 277 NSCLC (158 AC, 119 LSCC) and 20 NMLT samples.
RESULTS: We observed increased SATB1 immunoreactivity in NSCLC when compared to NMLT, and in LSCC when compared to AC cases. We also noted that an elevated SATB1 immunoreactivity was associated with a poor degree of AC differentiation, whereas in LSCC, an inverse relationship was observed. Our analyses revealed that the expression of SATB1 positively correlated with Ki-67 index in NSCLC and LSCC, but not in AC cases. Finally, we found that high SATB1 expression was associated with a better overall survival of patients with NSCLC.
CONCLUSION: SATB1 plays diverse roles in different NSCLC subtypes, and its expression may have a prognostic significance for patients with these tumours.

Li Y, Wang J, Yu M, et al.
SNF5 deficiency induces apoptosis resistance by repressing SATB1 expression in Sézary syndrome.
Leuk Lymphoma. 2018; 59(10):2405-2413 [PubMed] Related Publications
SNF5, is a core member of the SWI/SNF chromatin remodeling complex. It's deficiency leads to multiple types of aggressive cancer. Sézary syndrome, a leukemic variant of cutaneous T-cell lymphoma, is characterized by its resistance to apoptosis. Although the cause of apoptosis resistance is still poorly understood, recent evidence has revealed the importance of SATB1 in the apoptosis resistance of Sézary syndrome. In this study, we show that SNF5 is an upstream regulator of SATB1 in several conditions and that both are deficient in Sézary cells. Additionally, SNF5 not only controls the expression of SATB1, but also utilizes SATB1 to recruit itself to specific sites. Overexpression of SNF5 induces SATB1 expression and partially reverse apoptosis resistance phenotype in Sézary cells. These results suggest that both SNF5 and SATB1 may regulate apoptosis-related genes in Sézary syndrome. Thus, targeting SWI/SNF complex may represent a promising approach for Sézary syndrome therapy.

Frömberg A, Engeland K, Aigner A
The Special AT-rich Sequence Binding Protein 1 (SATB1) and its role in solid tumors.
Cancer Lett. 2018; 417:96-111 [PubMed] Related Publications
The Special AT-rich Sequence Binding Protein 1 (SATB1) exerts multiple functions, by influencing the structural organization of chromatin and interacting with several co-activators and co-repressors of transcription. Thus, SATB1 affects the expression of various genes by multiple mechanisms of action, involving three-dimensional chromatin architecture. More recently, SATB1 has been connected with solid tumors, tumorigenesis, tumor progression and tumor immunity. On the diagnostic side, SATB1 levels were found to correlate with clinicopathological features like increased TNM stage, reduced tumor differentiation, and a shorter overall survival. SATB1 expression was also identified as an independent prognostic marker in various cancers. Moreover, different gene knockdown or ectopic overexpression strategies in cancer cells have identified SATB1 to affect proliferation, cell cycle, apoptosis, cell morphology / cell polarity, EMT and multidrug-resistance as well as tumor formation, growth, invasion and metastasis in vivo. These processes are mediated through a great multitude of SATB1 target genes, including many (proto-) oncogenes. Functional and molecular studies on SATB1 in various cancers are comprehensively summarized, and the prospects and caveats of SATB1 as tumor marker and as putative target molecule are discussed.

Choudhary D, Clement JM, Choudhary S, et al.
SATB1 and bladder cancer: Is there a functional link?
Urol Oncol. 2018; 36(3):93.e13-93.e21 [PubMed] Related Publications
PURPOSE: SATB1, a global genome organizer, has been shown to play a role in the development and progression of some solid tumors, but its role in bladder cancer is undetermined. Moreover, there is conflicting data about the role of SATB1 in other tumors. This study was initiated to assess a potential role for SATB1 with the hypothesis that SATB1 acts as a tumor promoter in bladder cancer.
MATERIALS AND METHODS: We evaluated SATB1 expression in bladder cancer cell lines (HTB-5, HTB-9) and compared them to a benign urothelial cell line (UROtsa). Short-hairpin RNA was used to silence SATB1 in multiple cell lines, and cell death and cell proliferation were assessed using multiple assays.
RESULTS: SATB1 expression was increased significantly in all cancer cell lines compared to benign urothelial cells. SATB1 expression was knocked down by short-hairpin RNA and functional outcomes, including cell number, cell-cycle arrest, cell viability, and apoptosis after cisplatin treatment, were measured. Surprisingly, knockdown of SATB1 in 2 high-grade cancer cell lines showed opposing functional roles. Compared to the non-silencing control, HTB-5 cells, showed decreased cellular proliferation and increased sensitivity to cisplatin, whereas HTB-9 cells, showed increased cell numbers and increased resistance to cisplatin.
CONCLUSION: We conclude that our results in bladder cancer are consistent with the conflicting data reported in other cancers, and that SATB1 might have different roles in cancer dependent on genetic background and stage of the cancer.

Guo L, Zheng J, Yu T, et al.
Elevated expression of SATB1 is involved in pancreatic tumorigenesis and is associated with poor patient survival.
Mol Med Rep. 2017; 16(6):8842-8848 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
Special AT‑rich sequence‑binding protein 1 (SATB1) is a master chromatin organizer which has been reported to be implicated in tumor progression in breast and lung cancer. However, its functions in pancreatic tumorigenesis have yet to be elucidated. In the present study, the involvement of SATB1 in pancreatic cancer development was investigated in human BxPC‑3 pancreatic adenocarcinoma cells. Short hairpin (sh)RNA was used to stably downregulate SATB1 expression, and functional assays, including cell proliferation, colony formation, soft agar and migration assays, were performed in vitro. In addition, a mouse pancreatic cancer xenograft model was created to examine the tumor‑promoting properties of SATB1 in vivo. The present findings demonstrated that stable knockdown of SATB1 expression inhibited the proliferation, colony formation, anchorage‑independent growth and suppressed the migratory capabilities of BxPC‑3 cells in vitro. In addition, SATB1 downregulation significantly inhibited tumor growth in xenografted mice in vivo. Furthermore, SATB1 was revealed to be upregulated in human pancreatic cancer tissue samples compared with matched non‑cancerous adjacent tissues, and high SATB1 expression was associated with poor patient survival. Overall, the present study demonstrated that SATB1 promoted the proliferation of pancreatic cancer cells in vitro. In addition, SATB1 expression was revealed to be upregulated in human pancreatic cancer tissues and its upregulation was associated with poor patient survival. Therefore, SATB1 may have potential as a novel prognostic biomarker and therapeutic target for the treatment of patients with pancreatic cancer.

Xiao T, Fu L, Jie Z
SATB1 overexpression correlates with gastrointestinal neoplasms invasion and metastasis: a meta-analysis for Chinese population.
Oncotarget. 2017; 8(29):48282-48290 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
BACKGROUND: Gastrointestinal neoplasm (GIN) is the most common neoplasm in China. The global chromatin organizer SATB1 (special AT-rich sequence binding protein 1) is aberrantly expressed in multiple human neoplasms. We conducted this meta-analysis to investigate whether the invasion and metastasis of GIN correlates with SATB1 levels in tumor tissues in Chinese patients.
MATERIALS AND METHODS: Eligible studies were identified through multiple search strategies in the databases PubMed, Embase, Medline, CNKI, and WANFANG, and the relevant clinicopathological data were extracted. Data were pooled using the Mantel-Haenszel fixed-effects or DerSimonian-Laid random-effects model.
RESULTS: Fourteen studies consisting of 1622 patients were included. There were 3, 3, and 8 studies that evaluated esophageal, gastric, and colorectal cancers, respectively. The overall mean percentage of patients with elevated SATB1 levels was 47.84%. Among patients with GIN, SATB1 overexpression was associated with depth of invasion (T stage: RR 1.27, 95% CI 1.18-1.36, P = 0.000), regional lymph node metastasis (N stage: RR 1.51, 95% CI 1.22-1.87, P = 0.000), and distant metastasis (M stage: RR 2.54, 95% CI 1.46-4.41, P = 0.001). The tumor type most closely linked with invasion and metastasis in GIN was gastric cancer (RR for T stage: 1.64, RR for N stage: 1.68, RR for M stage: 3.15).
CONCLUSIONS: Invasion and metastasis of GIN in Chinese patients correlates with SATB1 overexpression in tumor tissues, most profoundly in gastric cancer.

Zhang S, Tong YX, Xu XS, et al.
Prognostic significance of SATB1 in gastrointestinal cancer: a meta-analysis and literature review.
Oncotarget. 2017; 8(29):48410-48423 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
BACKGROUND: The special AT-rich sequence-binding proteins 1 (SATB1) is a major regulator involved in cell differentiation. It has been shown that SATB1 acts as an oncogenic regulator. The clinical and prognostic significance of SATB1 in gastrointestinal cancer remains controversial. The purpose of this study is to conduct a systematic review and meta-analysis to elucidate the impact of SATB1 in gastrointestinal cancer.
RESULTS: A total of 3174 gastrointestinal cancer patients from 15 studies were included. The correlation between SATB1 expression and OS or RFS was investigated in 12 and 5 studies respectively. The results of meta-analysis showed that SATB1 overexpression is inversely correlated with OS (combined HR: 1.79, p = 0.0003) and RFS (combined HR: 2.46, p < 0.0001). In subgroup analysis, SATB1 expression is significantly correlated with poor prognosis in gastrointestinal cancer in Asian population. SATB1 expression is associated with stage, invasion depth, lymph node metastasis and distant metastasis.
METHODOLOGY: Published studies with data on overall survival (OS) and/or relapse free survival (RFS) and SATB1 expression were searched from Cochrane Library, PubMed and Embase (up to Dec 30, 2016). The outcome measurement is hazard ratio (HR) for OS or RFS related with SATB1 expression. Two reviewers independently screened the literatures, extracted the data and performed meta-analysis using RevMan 5.3.0 software. The combined HRs were calculated by fixed- or random-effect models.
CONCLUSIONS: The results of this meta-analysis suggest that SATB1 overexpression is related to advanced stage, lymph node metastasis and distant metastasis. SATB1 overexpression is a marker indicating poor prognosis in gastrointestinal cancer.

Ma J, Wu K, Zhao Z, et al.
Special AT-rich sequence binding protein 1 promotes tumor growth and metastasis of esophageal squamous cell carcinoma.
Tumour Biol. 2017; 39(3):1010428317694537 [PubMed] Related Publications
Esophageal squamous cell carcinoma is one of the most aggressive malignancies worldwide. Special AT-rich sequence binding protein 1 is a nuclear matrix attachment region binding protein which participates in higher order chromatin organization and tissue-specific gene expression. However, the role of special AT-rich sequence binding protein 1 in esophageal squamous cell carcinoma remains unknown. In this study, western blot and quantitative real-time polymerase chain reaction analysis were performed to identify differentially expressed special AT-rich sequence binding protein 1 in a series of esophageal squamous cell carcinoma tissue samples. The effects of special AT-rich sequence binding protein 1 silencing by two short-hairpin RNAs on cell proliferation, migration, and invasion were assessed by the CCK-8 assay and transwell assays in esophageal squamous cell carcinoma in vitro. Special AT-rich sequence binding protein 1 was significantly upregulated in esophageal squamous cell carcinoma tissue samples and cell lines. Silencing of special AT-rich sequence binding protein 1 inhibited the proliferation of KYSE450 and EC9706 cells which have a relatively high level of special AT-rich sequence binding protein 1, and the ability of migration and invasion of KYSE450 and EC9706 cells was distinctly suppressed. Special AT-rich sequence binding protein 1 could be a potential target for the treatment of esophageal squamous cell carcinoma and inhibition of special AT-rich sequence binding protein 1 may provide a new strategy for the prevention of esophageal squamous cell carcinoma invasion and metastasis.

Torkildsen S, Brunetti M, Gorunova L, et al.
Rearrangement of the Chromatin Organizer Special AT-rich Binding Protein 1 Gene,
Anticancer Res. 2017; 37(2):693-698 [PubMed] Related Publications
BACKGROUND/AIM: New chromosomal aberrations continue to be reported in acute myeloid leukemias (AML). The addition of more cases with the same genetic characteristics would establish an acquired aberration as a recurrent change, help determine its prognostic significance, and can provide insight into the mechanisms of leukemogenesis in patients with these rare abnormalities.
CASE REPORT: RNA-sequencing was performed on a patient with AML with the bone marrow karyotype 46,XY,t(3;5)(p24;q14)[5]/46,XY[10]. The translocation resulted in fusion of the SATB homeobox 1 gene (SATB1) (3p24) with an expression sequence tag with accession number BG503445 (5q14). The SATB1-BG503445 transcript may code for a SATB1 protein that would lack the C-terminal DNA-binding homeodomain.
CONCLUSION: The present study is the first to demonstrate rearrangement and disruption of SATB1 in AML. Rearrangements of chromosome band 3p24 were reported in 24 additional AMLs but not in known leukemia-specific chromosomal abnormalities. Further studies are needed to determine whether SATB1-BG503445 or other aberrations of SATB1 are recurrent in AML.

Song G, Liu K, Yang X, et al.
SATB1 plays an oncogenic role in esophageal cancer by up-regulation of FN1 and PDGFRB.
Oncotarget. 2017; 8(11):17771-17784 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
Esophageal cancer is a highly aggressive malignancy with very poor overall prognosis. Given the strong clinical relevance of SATB1 in esophagus cancer and other cancers suggested by previous studies, the exact function of SATB1 in esophagus cancer development is still unknown. Here we showed that the knockdown of SATB1 in esophageal cancer cell lines diminished the cell proliferation, survival and invasion. Whole genome transcriptome analysis of SATB1 knockdown cells revealed the different gene expression profiles between TE-1 cells and MDA-MB-231 cells. Network analysis and functional experiments further identified FN1 and PDGFRB to be key downstream genes regulated by SATB1 in esophageal cancer cells. Importantly, FN1 and PDGFRB were found to be highly expressed in human esophageal cancer. In summary, we provided the first molecular evidence that SATB1 played an oncogenic role in esophageal cancer by up-regulation of FN1 and PDGFRB.

Stephen TL, Payne KK, Chaurio RA, et al.
SATB1 Expression Governs Epigenetic Repression of PD-1 in Tumor-Reactive T Cells.
Immunity. 2017; 46(1):51-64 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
Despite the importance of programmed cell death-1 (PD-1) in inhibiting T cell effector activity, the mechanisms regulating its expression remain poorly defined. We found that the chromatin organizer special AT-rich sequence-binding protein-1 (Satb1) restrains PD-1 expression induced upon T cell activation by recruiting a nucleosome remodeling deacetylase (NuRD) complex to Pdcd1 regulatory regions. Satb1 deficienct T cells exhibited a 40-fold increase in PD-1 expression. Tumor-derived transforming growth factor β (Tgf-β) decreased Satb1 expression through binding of Smad proteins to the Satb1 promoter. Smad proteins also competed with the Satb1-NuRD complex for binding to Pdcd1 enhancers, releasing Pdcd1 expression from Satb1-mediated repression, Satb1-deficient tumor-reactive T cells lost effector activity more rapidly than wild-type lymphocytes at tumor beds expressing PD-1 ligand (CD274), and these differences were abrogated by sustained CD274 blockade. Our findings suggest that Satb1 functions to prevent premature T cell exhaustion by regulating Pdcd1 expression upon T cell activation. Dysregulation of this pathway in tumor-infiltrating T cells results in diminished anti-tumor immunity.

Frömberg A, Rabe M, Oppermann H, et al.
Analysis of cellular and molecular antitumor effects upon inhibition of SATB1 in glioblastoma cells.
BMC Cancer. 2017; 17(1):3 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
BACKGROUND: The Special AT-rich Sequence Binding Protein 1 (SATB1) regulates the expression of many genes by acting as a global chromatin organizer. While in many tumor entities SATB1 overexpression has been observed and connected to pro-tumorigenic processes, somewhat contradictory evidence exists in brain tumors with regard to SATB1 overexpression in glioblastoma and its association with poorer prognosis and tumor progression. On the functional side, initial data indicate that SATB1 may be involved in several tumor cell-relevant processes.
METHODS: For the detailed analysis of the functional relevance and possible therapeutic potential of SATB1 inhibition, we employ transient siRNA-mediated knockdown and comprehensively analyze the cellular and molecular role of SATB1 in glioblastoma.
RESULTS: In various cell lines with different SATB1 expression levels, a SATB1 gene dose-dependent inhibition of anchorage-dependent and -independent proliferation is observed. This is due to cell cycle-inhibitory and pro-apoptotic effects of SATB1 knockdown. Molecular analyses reveal SATB1 knockdown effects on multiple important (proto-) oncogenes, including Myc, Bcl-2, Pim-1, EGFR, β-catenin and Survivin. Molecules involved in cell cycle, EMT and cell adhesion are affected as well. The putative therapeutic relevance of SATB1 inhibition is further supported in an in vivo tumor xenograft mouse model, where the treatment with polymeric nanoparticles containing SATB1-specific siRNAs exerts antitumor effects.
CONCLUSION: Our results demonstrate that SATB1 may represent a promising target molecule in glioblastoma therapy whose inhibition or knockdown affects multiple crucial pathways.

Komisarof J, McCall M, Newman L, et al.
A four gene signature predictive of recurrent prostate cancer.
Oncotarget. 2017; 8(2):3430-3440 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
Prostate cancer is the most common form of non-dermatological cancer among US men, with an increasing incidence due to the aging population. Patients diagnosed with clinically localized disease identified as intermediate or high-risk are often treated by radical prostatectomy. Approximately 33% of these patients will suffer recurrence after surgery. Identifying patients likely to experience recurrence after radical prostatectomy would lead to improved clinical outcomes, as these patients could receive adjuvant radiotherapy. Here, we report a new tool for prediction of prostate cancer recurrence based on the expression pattern of a small set of cooperation response genes (CRGs). CRGs are a group of genes downstream of cooperating oncogenic mutations previously identified in a colon cancer model that are critical to the cancer phenotype. We show that systemic dysregulation of CRGs is also found in prostate cancer, including a 4-gene signature (HBEGF, HOXC13, IGFBP2, and SATB1) capable of differentiating recurrent from non-recurrent prostate cancer. To develop a suitable diagnostic tool to predict disease outcomes in individual patients, multiple algorithms and data handling strategies were evaluated on a training set using leave-one-out cross-validation (LOOCV). The best-performing algorithm, when used in combination with a predictive nomogram based on clinical staging, predicted recurrent and non-recurrent disease outcomes in a blinded validation set with 83% accuracy, outperforming previous methods. Disease-free survival times between the cohort of prostate cancers predicted to recur and predicted not to recur differed significantly (p = 1.38x10-6). Therefore, this test allows us to accurately identify prostate cancer patients likely to experience future recurrent disease immediately following removal of the primary tumor.

Li YC, Bu LL, Mao L, et al.
SATB1 promotes tumor metastasis and invasiveness in oral squamous cell carcinoma.
Oral Dis. 2017; 23(2):247-254 [PubMed] Related Publications
OBJECTIVE: Our aim is to evaluate the expression of SATB1 in human oral squamous cell carcinomas (OSCC) and its role in the invasiveness and metastasis of OSCC.
SUBJECTS AND METHODS: A human OSCC tissue microarray was used to evaluate the expression pattern of SATB1. SATB1 mRNA knockdown was performed in human OSCC cell lines SCC25 and Cal27 to assess the function of SATB1 in the invasiveness and metastasis of OSCC.
RESULTS: SATB1 is highly expressed in human OSCC determined by immunohistochemistry, and its nuclear/cytoplasmic ratio of histoscore is significantly correlated with patients' prognosis. Reduced cell motility, invasiveness, expression of epithelial to mesenchymal transition (EMT) markers (N-cadherin and β-catenin), and elevated expression of epithelial markers were observed in SATB1-knockdown cells in in vitro studies. Depletion of SATB1 also restored a cobblestone-like morphology in TGF-β1-treated cells.
CONCLUSIONS: These findings suggest SATB1 may play an important role in OSCC invasiveness and metastasis.

Lee JJ, Kim M, Kim HP
Epigenetic regulation of long noncoding RNA UCA1 by SATB1 in breast cancer.
BMB Rep. 2016; 49(10):578-583 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
Special AT-rich sequence binding protein 1 (SATB1) is a nuclear matrix-associated DNA-binding protein that functions as a chromatin organizer. SATB1 is highly expressed in aggressive breast cancer cells and promotes growth and metastasis by reprograming gene expression. Through genomewide cross-examination of gene expression and histone methylation, we identified SATB1 target genes for which expression is associated with altered epigenetic marks. Among the identified genes, long noncoding RNA urothelial carcinoma-associated 1 (UCA1) was upregulated by SATB1 depletion. Upregulation of UCA1 coincided with increased H3K4 trimethylation (H3K4me3) levels and decreased H3K27 trimethylation (H3K27me3) levels. Our study showed that SATB1 binds to the upstream region of UCA1 in vivo, and that its promoter activity increases with SATB1 depletion. Furthermore, simultaneous depletion of SATB1 and UCA1 potentiated suppression of tumor growth and cell survival. Thus, SATB1 repressed the expression of oncogenic UCA1, suppressing growth and survival of breast cancer cells. [BMB Reports 2016; 49(10): 578-583].

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