SATB1 Overexpression Regulates the Development and Progression in Bladder Cancer through EMT

Abstract

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.

High expression of special AT‑rich sequence binding protein‑1 predicts esophageal squamous cell carcinoma relapse and poor prognosis

“…Previous studies have indicated that SATB1 is associated with prognosis in resected upper gastrointestinal tract adenocarcinoma and other tumor forms (20,23,24). Data from the present study revealed that patients with higher SATB1 mRNA expression had a higher rate of relapse.…”

SATB1 plays an oncogenic role in esophageal cancer by up-regulation of FN1 and PDGFRB

“…It is already known that SATB1 is an oncogene which promotes breast tumor growth and metastasis [6]; its expression was reported in several breast cancer cell lines and tumor biopsies [7–9]. The association of SATB1 was also observed in several other cancers [9], including colorectal cancer [10–12], prostate cancer [13, 14], endometriod endometrial cancer [15, 16], liver cancer [17], rectal cancer [18], bladder cancer [19], ovarian cancer [20] and gastric cancer [21]. …”

SATB1 promotes tumor metastasis and invasiveness in oral squamous cell carcinoma

“…Notably, we have demonstrated that tumors expressed higher levels of SATB1 metastasized to more lymph nodes, which supports the links between SATB1 and metastasis of OSCC. Indeed, many pieces of researches have reported its pro‐metastatic role in various other cancers (Chu et al , ; Han et al , ; Huang et al , ; Mao et al , ; Shen et al , ; Shukla et al , ; Zhang et al , , ; Elebro et al , ; Liu et al , ; Lv et al , ; Wan et al , ). Interestingly, our data have shown that OSCC tumor cells that have migrated to lymph node express even higher levels of SATB1.…”

“…Accumulating evidence suggested tumor cells that undergo EMT acquired better survival and metastatic capabilities. A few papers have reported a potential link between SATB1 and the initiation of EMT (Li et al , ; Cheng et al , ; Wan et al , ). In consistent with these findings, our data showed knockdown of SATB1 significantly reduced the expression of EMT‐related proteins, as well as cell invasiveness and motility.…”

“…Using a human breast cancer cell xenograft mice model, they demonstrated that SATB1 regulated a large array of gene expressions in cancer cells, thus functioning as a determinant for breast cancer metastasis (Cai et al , ). It has also been observed that SATB1 promoted the metastasis of other numerous types of cancer, including glioma, small cell lung cancer, and renal cell carcinoma (Chu et al , ; Han et al , ; Huang et al , ; Mao et al , ; Shen et al , ; Shukla et al , ; Zhang et al , , ; Elebro et al , ; Liu et al , ; Lv et al , ; Wan et al , ). The expression and clinical significance of SATB1 in OSCC have not yet been reported.…”