Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
J Cell Mol Med. 2020 Oct;24(19):11064-11069. doi: 10.1111/jcmm.15755. Epub 2020 Sep 4.
Several studies have confirmed the involvement of cancer stem cells (CSC) in tumour progression, metastasis, drug resistance and cancer relapse. SATB2 (special AT-rich binding protein-2) acts as a transcriptional co-factor and modulates chromatin architecture to regulate gene expression. The purpose of this review was to discuss the pathophysiological roles of SATB2 and assess whether it could be used as a therapeutic target for cancer. SATB2 modulated the expression of those genes which regulated pluripotency and self-renewal. Overexpression of SATB2 gene in normal epithelial cells was shown to induce transformation, as a result transformed cells gained CSC's characteristics by expressing stem cell markers and pluripotency maintaining factors, suggesting its role as an oncogene. In addition, SATB2 induced epithelial-mesenchymal transition (EMT) and metastasis. Interestingly, the expression of SATB2 was positively correlated with the activation of β-catenin/TCF-LEF pathway. Furthermore, SATB2 silencing inhibited EMT and their positive regulators, and tumour growth, and suppressed the expression of stem cell markers, pluripotency maintaining factors, cell cycle and cell survival genes, and TCF/LEF targets. Based on the cancer genome atlas (TCGA) expression data and published papers, SATB2 alone or in combination with other proteins could be used a diagnostic biomarker for cancer. Although there is no pharmacological inhibitor of SATB2, studies using genetic approaches suggest that SATB2 could be a potential target for cancer treatment and prevention.
已有多项研究证实，癌症干细胞（CSC）参与肿瘤的演进、转移、耐药和癌症复发。SATB2（特异性富含 AT 的结合蛋白 2）作为转录共因子，调节染色质结构以调控基因表达。本文旨在讨论 SATB2 的病理生理作用，并评估其是否可作为癌症的治疗靶点。SATB2 调节那些调节多能性和自我更新的基因的表达。研究表明，正常上皮细胞中 SATB2 基因的过表达可诱导转化，转化细胞通过表达干细胞标志物和维持多能性的因子获得 CSC 的特征，提示其作为癌基因的作用。此外，SATB2 诱导上皮-间充质转化（EMT）和转移。有趣的是，SATB2 的表达与β-catenin/TCF-LEF 通路的激活呈正相关。此外，SATB2 沉默抑制 EMT 及其阳性调节因子、肿瘤生长，并抑制干细胞标志物、维持多能性的因子、细胞周期和细胞存活基因以及 TCF/LEF 靶基因的表达。基于癌症基因组图谱（TCGA）的表达数据和已发表的论文，SATB2 单独或与其他蛋白联合可作为癌症的诊断生物标志物。虽然目前尚无 SATB2 的药理学抑制剂，但使用遗传方法的研究表明，SATB2 可能是癌症治疗和预防的潜在靶点。
