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SATB1

The global gene regulator Special AT-rich sequence-binding protein-1 (SATB1) has been reported to induce EMT-like changes and be associated with poor clinical outcome in several cancers. This study aims to evaluate whether SATB1 affects the biological behaviors of bladder transitional cell carcinoma (BTCC) and further elucidate if this effect works through an epithelial-mesenchymal transition (EMT) pathway. The expression of SATB1, E-cadherin (epithelial markers), vimentin (mesenchymal markers) in BTCC tissues and adjacent noncancerous tissues, as well as in two cell lines of bladder cancer were investigated. Whether the SATB1 expression is associated with clinicopathological factors or not was statistically analyzed. Cell invasion and migration, cell cycle, cell proliferation and apoptosis were evaluated in SATB1 knockdown and overexpressed cell lines. Our results showed that the expression of SATB1 was remarkably up-regulated both in BTCC tissues and in bladder cancer cell lines with high potential of metastasis. The results were also associated with EMT markers and poor prognosis of BTCC patients. Moreover, SATB1 induced EMT processes through downregulation of E-cadherin, upregulation of E-cadherin repressors (Snail, Slug and vimentin). SATB1 also promoted cell cycle progression, cell proliferation, cell invasion and cell migration, but did not alter cell survival. In conclusion, our results suggest that SATB1 plays a crucial role in the progression of bladder cancer by regulating genes controlling EMT processes. Further, it may be a novel therapeutic target for aggressive bladder cancers.

SATB1, a global gene regulator, has been implicated in the growth and metastasis of multiple cancers, including colorectal cancer. While the understanding about the role of SATB1 in CRC remains limited. The aim of our study is to investigate the expression of SATB1 in CRC, and the relationship between SATB1 expression pattern and clinicopathological variables. A further aim is to analyze the correlation between SATB1 expression and epithelial-mesenchymal transition in CRC. Immunohistochemical expression of SATB1, beta-catenin, E-cadherin, CK20, Vimentin, SMA, and desmin were assessed in a cohort of 200 patients using tissue microarrays. SATB1 was expressed in 133 (66.5%) CRC primary lesions, 14 (28%) adjacent colorectal mucosa specimens, and 60 (75%) corresponding lymph node metastases. The expression level of SATB1 was significantly higher in lymph node metastases than in CRC primary lesions and normal mucosa (P = 0.000). High expression of SATB1 in CRC was strongly correlated with poor differentiation of tumor tissues (P = 0.000). High expression of SATB1 was significantly correlated with aberrant expression of beta-catenin (P = 0.0005), low expression of E-cadherin (P = 0.000) and CK20 (P = 0.000) and with high expression of Vimentin (P = 0.001). No SMA or desmin protein was expressed in the CRC cells. Our results suggested that high expression of SATB1 is significantly correlated with poor differentiation of CRC. SATB1 might promote the epithelial-mesenchymal transition by increasing the aberrant expression of beta-catenin.

Special AT-rich sequence binding protein 1 (SATB1) plays important role in the regulation of chromatin structure and gene expression. Recent studies have indicated oncogenic role of SATB1. However, the function of SATB1 in prostate cancer progression and metastasis remains unclear. In this study SATB1 expression vector or siRNA was employed to modulate the expression level of SATB1 in prostate cancer cells and xenograft tumor in nude mouse model. Immunohistochemical analysis was performed on clinical prostate cancer samples. Silencing SATB1 inhibited the growth of DU-145 cells subcutaneous tumor in nude mice, while SATB1 overexpression promoted the growth of LNCaP cells subcutaneous tumor in nude mice. Immunohistochemical and Western blot analysis of the xenografts showed that silencing SATB1 led to decreased expression of vimentin and MMP2 and increased expression of E-cadherin, while SATB1 overexpression led to increased expression of vimentin and MMP2 and decreased expression of E-cadherin. Furthermore, SATB1, vimentin and MMP2 expression was increased significantly while E-cadherin expression was reduced significantly in clinical samples of prostate carcinoma with metastasis compared to prostate carcinoma without metastasis and benign prostate hyperplasia. Taken together, these findings suggest that the modulation of epithelial-mesenchymal transition by SATB1 may contribute to prostate cancer metastasis.CI - Copyright (c) 2016 Elsevier Masson SAS. All rights reserved.

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.CI - Copyright (c) 2018 Elsevier B.V. All rights reserved.