6304

SATB1

SATB homeobox 1;SATB1;SATB homeobox 1

DNA-binding protein SATB1|special AT-rich sequence binding protein 1 (binds to nuclear matrix/scaffold-associating DNA)|special AT-rich sequence-binding protein 1

3p23

protein-coding

OBJECTIVE: To detect the expression of special AT-rich sequence-binding protein (SATB1) in bladder urothelial carcinoma and investigate its correlation to the biological behavior of the carcinoma. METHODS: The expression of SATB1 mRNA was detected in 34 cases of bladder urothelial carcinoma and 14 normal bladder tissues by RT-PCR, and the protein expression of SATB1 was detected in 68 cases of bladder urothelial carcinoma and 17 normal bladder tissues by immunohistochemistry. The correlation between SATB1 expressions and the biological behavior of the tumor was analyzed. RESULTS: The expression of SATB1 was significantly higher in bladder urothelial carcinoma tissues than in normal bladder tissues (P<0.05). and the expression of SATB1 in the tumor tissues was correlated to the clinical stage and metastasis of the tumor. CONCLUSION: SATB1 expression can be associated with the development and metastasis of bladder urothelial carcinoma and may potentially serve as an indicator for predicting the prognosis of bladder urothelial carcinoma.

Mechanisms underlying global changes in gene expression during tumour progression are poorly understood. SATB1 is a genome organizer that tethers multiple genomic loci and recruits chromatin-remodelling enzymes to regulate chromatin structure and gene expression. Here we show that SATB1 is expressed by aggressive breast cancer cells and its expression level has high prognostic significance (P < 0.0001), independent of lymph-node status. RNA-interference-mediated knockdown of SATB1 in highly aggressive (MDA-MB-231) cancer cells altered the expression of >1,000 genes, reversing tumorigenesis by restoring breast-like acinar polarity and inhibiting tumour growth and metastasis in vivo. Conversely, ectopic SATB1 expression in non-aggressive (SKBR3) cells led to gene expression patterns consistent with aggressive-tumour phenotypes, acquiring metastatic activity in vivo. SATB1 delineates specific epigenetic modifications at target gene loci, directly upregulating metastasis-associated genes while downregulating tumour-suppressor genes. SATB1 reprogrammes chromatin organization and the transcription profiles of breast tumours to promote growth and metastasis; this is a new mechanism of tumour progression.

Evaluation of: Han HJ, Russo J, Kohwi Y et al.: SATB1 reprogrammes gene expression to promote breast tumor growth and metastasis. Nature 452(7184), 187-193 (2008). metastasis is the most common cause of death in cancer patients. However, the genetic mechanisms involved in the master control genes of metastasis remain unclear. In this study, the authors found that special AT-rich sequence-binding protein 1 (SATB1) expression contributed to breast cancer growth and metastasis. SATB1 expression is detected in aggressive breast cancer cells rather than nonaggressive breast cancer cells. Moreover, by introducing the SATB1 gene into nonmetastatic breast cancer cells, invasive tumors can be induced in mice; whereas, silencing of SATB1 in metastatic cells not only abolishes metastasis and tumor growth in mice, but also returns cells to their normal appearance. These effects are related as SATB1 upregulates metastasis-associated genes while downregulating tumor-suppressor genes through epigenetic modification. The research suggests that SATB1 is a master regulator in the metastasis of breast cancer and, therefore, can be considered as an independent prognostic factor and a potential therapeutic target for breast cancer.

When cells change functions or activities (such as during differentiation, response to extracellular stimuli, or migration), gene expression undergoes large-scale reprogramming, in cell type- and function-specific manners. Large changes in gene regulation require changes in chromatin architecture, which involve recruitment of chromatin remodeling enzymes and epigenomic modification enzymes to specific genomic loci. Transcription factors must also be accurately assembled at these loci. SATB1 is a genome organizer protein that facilitates these processes, providing a nuclear architectural platform that anchors hundreds of genes, through its interaction with specific genomic sequences; this activity allows expression of all these genes to be regulated in parallel, and enables cells to thereby alter their function. We review and describe future perspectives on SATB1 function in higher-order chromatin structure and gene regulation, and its role in metastasis of breast cancer and other tumor types.

AIM: To evaluate the expression of special AT-rich sequence-binding protein 1 (SATB1) gene in colorectal cancer and its role in colorectal cancer cell proliferation and invasion. METHODS: Immunohistochemistry was used to detect the protein expression of SATB1 in 30 colorectal cancer (CRC) tissue samples and pair-matched adjacent non-tumor samples. Cell growth was investigated after enhancing expression of SATB1. Wound-healing assay and Transwell assay were used to investigate the impact of SATB1 on migratory and invasive abilities of SW480 cells in vitro. Nude mice that received subcutaneous implantation or lateral tail vein were used to study the effects of SATB1 on tumor growth or metastasis in vivo. RESULTS: SATB1 was over-expressed in CRC tissues and CRC cell lines. SATB1 promotes cell proliferation and cell cycle progression in CRC SW480 cells. SATB1 overexpression could promote cell growth in vivo. In addition, SATB1 could significantly raise the ability of cell migration and invasion in vitro and promote the ability of tumor metastasis in vivo. SATB1 could up-regulate matrix metalloproteases 2, 9, cyclin D1 and vimentin, meanwhile SATB1 could down-regulate E-cadherin in CRC. CONCLUSION: SATB1 acts as a potential growth and metastasis promoter in CRC. SATB1 may be useful as a therapeutic target for CRC.

Special AT-rich sequence binding protein 1 (SATB1), a new type of gene regulator, has been reported to express in various human cancers and may associate with the malignant potential. However, there are few data available on SATB1 expression and its relationship to tumor progression in gastric cancer. The current study was designed to examine the SATB1 expression in gastric cancer and to correlate it with clinical outcome. SATB1 expression was studied by qRT-PCR, western blotting and immunohistochemistry, respectively. The correlations between SATB1 expression and clinicopathological factors were statistically analyzed. SATB1 mRNA expression was significantly up-regulated in gastric cancer specimens as compared with that in normal tissues (P<0.001). Overexpression of SATB1 protein was observed in gastric cancer cell lines by western blotting. Fifty-three (44.9%) cases showed positive staining for the SATB1 proteins by immunohistochemistry. The expression of SATB1 mRNA agreed well with the western blotting and immunohistochemical findings (P<0.001). SATB1 expression was positively correlated with age, depth of invasion, lymph node metastasis, distant metastasis and TNM stage. Moreover, Kaplan-Meier analysis revealed that SATB1 overexpression was associated with a significantly worse survival (P<0.001). Further multivariable analysis indicated that SATB1 expression was an independent prognostic indicator for gastric cancer (P=0.023). In summary, overexpression of SATB1 correlated with metastatic potential of human gastric cancer and would be a novel independent prognostic marker for predicting the outcome of gastric cancer.

OBJECTIVE: To investigate the expression of special AT-rich sequence binding protein 1 (SATB1) mRNA in hepatocellular carcinoma (HCC) and explore its correlation to the clinicopathological features, surgical outcomes and metastasis of HCC. METHODS: The total RNA was extracted from 102 HCC tissues and the adjacent tissues, and the expression of SATB1 mRNA was detected using quantitative real-time PCR. The correlations of SATB1 mRNA expression to the clinicopathological features, postoperative recurrence and metastasis of the tumor were analyzed. RESULTS: The expression of SATB1 mRNA in HCC tissues was 3.27 folds higher than that in the adjacent tissues (P<0.001). The expression of SATB1 mRNA in HCC was associated with liver cirrhosis, AFP level, tumor size, tumor thrombi, histological differentiation, TNM classification, postoperative recurrence and metastasis (P<0.05), but not to the patients' gender, age, HbsAg positivity, HCV-Ab positivity, tumor number, or the presence of tumor encapsulation (P>0.05). In patients with significant high expression, high expression, and low expression of SATB1 mRNA, the postoperative recurrence rates were 82.68%, 0, and 0, with the 3-year survival rate of 0, 52.63%, and 100%, respectively. CONCLUSION: SATB1 mRNA expression is associated with the postoperative recurrence and metastasis of HCC, and can be used as an indicator for predicting the recurrence and metastasis of HCC.

BACKGROUND: Special AT-rich binding protein-1 (SATB1) reprograms chromatin organization and transcription profiles to promote tumour growth and metastasis. AIMS: This study aimed to confirm the effects of SATB1 on the growth and metastasis of liver cancer and its specific regulation mechanism. METHODS: SATB1 expression was evaluated in human hepatoma tissue, adjacent noncancerous tissue and seven kinds of liver cancer cell lines. Cell cycle, cell proliferation, apoptosis and epithelial-mesenchymal transition (EMT) was investigated after enhanced or silenced expression of SATB1. The regulatory action of SATB1 on the expression of genes that are known to regulate cell cycle progression, apoptosis and EMT and the specific apoptotic pathway on which it acts were further analysed. Nude mice that received subcutaneous implantation were used to study the effects of SATB1 on tumour growth in vivo. RESULTS: Our data show that the high expression of SATB1 was observed in the human hepatocellular carcinoma tissue (26/45) and liver cancer cell lines with high metastatic potential. SATB1 upregulated CDK4 and downregulated p16 (INK) (4A) to promote cell cycle progression and cell proliferation and prevented apoptosis by inhibiting the FADD-caspase-8-caspase-3 death receptor-mediated apoptosis pathway. SATB1 also induced EMT concomitant with increased expression of Snail1, Slug, Twist and vimentin and decreased expression of E-cadherin, tight junction protein ZO-1 and desmoplakin. SATB1 promoted the growth of tumour in vivo. CONCLUSION: These data suggest that the SATB1 gene may play an important role in the development and progression of liver cancer by regulation of genes related to cell cycle progression, apoptosis and EMT.

BACKGROUND: Special AT-rich sequence-binding protein-1 (SATB1), a new type of gene regulator, has been reported to be expressed in several human cancers and may have malignant potential. However, no data on SATB1 expression and its relationship to tumor progression in cutaneous malignant melanoma (CMM) has yet been reported. OBJECTIVE: We examined the immunohistochemical expression of SATB1 in CMM to determine whether it could serve as a prognostic marker. METHODS: A total of 97 samples of primary CMM and controls were immunostained for SATB1. The following clinicopathologic variables were evaluated: age, gender, subtype, SATB1 expression, Breslow thickness, Clark level, presence of ulceration, lymph node metastasis, distant metastasis, and survival. Statistical analyses were performed to assess for associations. Several parameters were analyzed for survival using the Kaplan-Meier method and Cox proportional-hazards model. RESULTS: Forty cases (85.1%) of CMM showed positive staining for SATB1 by immunohistochemistry. The intensity of SATB1 staining was significantly higher in CMM than in nevus NV and normal skin (NS) (P < 0.01). High SATB1 expression was significantly correlated with Breslow thickness, Clark level, mortality, presence of ulceration, and lymph node metastasis (P < 0.01). Moreover, Kaplan-Meier analysis revealed that SATB1 overexpression was significantly associated with worse survival (P < 0.01). Further univariate analysis and multivariate regression analysis indicated that SATB1 expression was an independent prognostic marker for CMM (P = 0.03). CONCLUSIONS: The overexpression of SATB1 correlated with metastatic potential of CMM and is a novel independent prognostic marker for predicting outcome.

OBJECTIVE: To study the expression and clinical significance of SATB1, BRMS1 in Ovarian serous adenocarcinoma. METHODS: Immanohistochemistrical SP method was used to detect the expression of SATB1, BRMS1 in 11 cases of normal ovarian tissue and 11 cases of benign ovarian tumor and 10 cases of ovarian borderline tumor and 53 cases ovarian serous adenocarcinoma. RESULTS: The expression of SATB1 in ovarian serous adenocarcinoma (86.8%) was significantly higher than those of normal ovarian tissues (0) and benign ovarian tumor tissues (36.4%), P < 0.05, and there was no difference between ovarian borderline tumor (70%) and ovarian serous adenocarcinoma, P > 0.05. The expression of BRMS1 in ovarian serous adenocarcinoma (28. 3%) was significantly lower than those in normal ovarian tissues (100%) and benign ovarian tumor tissues (81.8%), P < 0. 05, and there was no difference between ovarian borderline tumor (60%) and ovarian serous adenocarcinoma, P > 0.05. The inverse correlation between the expression of SATB1 and BRMS1 was observed (r = -0.387, P < 0.05). The expression of SATB1 was correlated with surgical stage and lymph node metastasis (P < 0.05), BRMS1 was correlated with surgical stage, lymph node metastasis and tumor size (P < 0.05); SATB1 and BRMS1 had no correlation with the patients whether menopause or not, histopathological grading, ascites (P > 0.05). CONCLUSION: SATB1 and BRMS1 might play an important role in the development and lymph node metastasis of ovarian cancer.

BACKGROUND: Special AT-rich sequence binding protein 1 (SATB1) is a nuclear factor that functions as the global chromatin organizer to regulate chromatin structure and gene expression gene expression. SATB1 has been shown to be abnormally expressed in various types of cancer. However, the expression and role of SATB1 in prostate cancer remain unclear. METHODS: 120 cases of prostatic carcinoma and 60 cases of benign prostate hyperplasia were analyzed for SATB1 expression by immunohistochemistry. LNCaP, DU-145, and PC3 prostate cancer cells were examined for SATB1 expression by Western blot analysis. Cell proliferation and invasion was evaluated by CCK8 and transwell invasion assay, respectively. RESULTS: SATB1 staining was stronger in prostatic carcinomas with metastasis than in those without metastasis, but was absent in benign prostate hyperplasia. Furthermore, SATB1 expression was positively correlated with bone metastasis and the Gleason score. SATB1 overexpression promoted the proliferation and invasion of LNCaP cells while SATB1 knockdown inhibited the proliferation and invasion of DU-145 cells. CONCLUSIONS: These findings provide novel insight into oncogenic role of SATB1 in prostate cancer, suggesting that SATB1 is a promising biomarker and therapeutic target for prostate cancer.