SATB1 promotes epithelial-mesenchymal transition and metastasis in prostate cancer

Abstract

Special AT-rich sequence-binding protein-1 (SATB1) is associated with cancer progression and poor clinical outcome. The present study aims to evaluate whether SATB1 affects the biological behaviors of prostate cancer (PCa), and furthermore, to elucidate whether this effect works through the epithelial-mesenchymal transition (EMT) pathway. Firstly, the expression of SATB1 was investigated in a series of PCa tissues as well as in a panel of PCa cell lines. Cell proliferation, migration and invasion were evaluated in SATB1 knockdown and overexpressed PCa cell lines by MTT and Transwell assays. The results showed that the expression of SATB1 was markedly upregulated in PCa tissues and all PCa cell lines (P<0.001). Ectopic expression of SATB1 promoted PCa cell proliferation and migration. Knockdown of SATB1 repressed the ability of cell proliferation and migration of PCa cells. In addition, inhibition of SATB1 could reverse the EMT processes through upregulation of E-cadherin and downregulation of vimentin. The present study provided evidence that SATB1 may act as a potential therapeutic target in PCa patients.

Functional relevance of SATB1 in immune regulation and tumorigenesis

“…Since the discovery of SATB1, its role in the pathogenesis of various cancers has been investigated. Importantly, upregulation of SATB1 has been shown to promote many pathological features across a wide range of cancers [38,39] including breast [1,[40][41][42], colorectal [2,[43][44][45], lung [46,47], nasopharyngeal [48], oesophageal [3,49,50], gastric [51,52], pancreatic [53,54], ovarian [32,55,56], liver [57][58][59], prostate [60][61][62][63], bladder [64,65], and brain [66][67][68][69][70]. In most cancers, the SATB1 expression is positively associated with increased tumour size, lymph node involvement and metastasis [71,72], tumour progression [1,2], poor prognosis [50,56] and reduced overall survival [49,54].…”

“…As a key inducer of EMT, the transcription factor Snail, plays an important role in embryonic development and cancer progression by repressing the expression of E-cadherin [98]. SATB1 was shown to downregulate E-cadherin expression and upregulate inducers of EMT such as Snail1, Slug, Twist and vimentin in hepatocellular bladder and prostate cancers [59,62,65]. SATB1 also promoted drug-induced EMT in breast cancer cell lines, driven by the positive feedback regulation of miR-448 and NF-κB signalling [99].…”

LINC01016 promotes the malignant phenotype of endometrial cancer cells by regulating the miR-302a-3p/miR-3130-3p/NFYA/SATB1 axis

“…SATB1 is a nuclear matrix attachment region-binding protein that recently emerged as a new regulator of oncogenic pathways 26 . SATB1 was demonstrated to be involved in a variety of cancers, and its transcript level was obviously upregulated during endometrial carcinogenesis 27 . We predicted that NFYA could act as a transcriptional factor of SATB1 and the promotor of SATB1 would contain a putative CCAAT sequence to which NFYA could bind.…”

MicroRNA‑100 functions as a tumor suppressor in cervical cancer via downregulating the SATB1 expression and regulating AKT/mTOR signaling pathway and epithelial‑to‑mesenchymal transition

“…SATB1 has been reported to be involved in the metastasis and growth of numerous malignant tumors. For example, Qi et al (16) indicated that SATB1 promoted EMT and metastases in prostate cancer; Li et al (17) found that SATB1 facilitated tumor oral squamous cell carcinoma metastases and invasiveness; studies by Pan et al (18) demonstrated that SATB1 was correlated with metastasis and progression of breast carcinoma. These studies suggested that SATB1 exerted oncogenic roles in tumor progression.…”