Kansas City VA Medical Center, 4801 Linwood Boulevard, Kansas City, MO 66128, USA.
Department of Chemistry and Biochemistry, Baylor University, Waco, TX 76798, USA.
Cells. 2024 Jun 3;13(11):962. doi: 10.3390/cells13110962.
Special AT-rich sequence binding protein-2 (SATB2) is a nuclear matrix protein that binds to nuclear attachment regions and is involved in chromatin remodeling and transcription regulation. In stem cells, it regulates the expression of genes required for maintaining pluripotency and self-renewal and epithelial-mesenchymal transition (EMT). In this study, we examined the oncogenic role of SATB2 in prostate cancer and assessed whether overexpression of SATB2 in human normal prostate epithelial cells (PrECs) induces properties of cancer stem cells (CSCs). The results demonstrate that SATB2 is highly expressed in prostate cancer cell lines and CSCs, but not in PrECs. Overexpression of SATB2 in PrECs induces cellular transformation which was evident by the formation of colonies in soft agar and spheroids in suspension. Overexpression of SATB2 in PrECs also resulted in induction of stem cell markers (CD44 and CD133), pluripotency-maintaining transcription factors (cMYC, OCT4, SOX2, KLF4, and NANOG), CADHERIN switch, and EMT-related transcription factors. Chromatin immunoprecipitation assay demonstrated that SATB2 can directly bind to promoters of BCL-2, BSP, NANOG, MYC, XIAP, KLF4, and HOXA2, suggesting SATB2 is capable of directly regulating pluripotency/self-renewal, cell survival, and proliferation. Since prostate CSCs play a crucial role in cancer initiation, progression, and metastasis, we also examined the effects of SATB2 knockdown on stemness. SATB2 knockdown in prostate CSCs inhibited spheroid formation, cell viability, colony formation, cell motility, migration, and invasion compared to their scrambled control groups. SATB2 knockdown in CSCs also upregulated the expression of E-CADHERIN and inhibited the expression of N-CADHERIN, SNAIL, SLUG, and ZEB1. The expression of SATB2 was significantly higher in prostate adenocarcinoma compared to normal tissues. Overall, our data suggest that SATB2 acts as an oncogenic factor where it is capable of inducing malignant changes in PrECs by inducing CSC characteristics.
富含特殊 AT 的序列结合蛋白 2（SATB2）是一种核基质蛋白，可与核附着区域结合，并参与染色质重塑和转录调控。在干细胞中，它调节维持多能性和自我更新以及上皮-间充质转化（EMT）所需的基因的表达。在这项研究中，我们研究了 SATB2 在前列腺癌中的致癌作用，并评估了 SATB2 在人正常前列腺上皮细胞（PrEC）中的过表达是否诱导癌症干细胞（CSC）的特性。结果表明，SATB2 在前列腺癌细胞系和 CSC 中高度表达，但在 PrEC 中不表达。SATB2 在 PrEC 中的过表达诱导细胞转化，这通过软琼脂中的集落形成和悬浮中的球体形成明显。SATB2 在 PrEC 中的过表达还导致干细胞标志物（CD44 和 CD133）、多能性维持转录因子（cMYC、OCT4、SOX2、KLF4 和 NANOG）、钙粘蛋白转换和 EMT 相关转录因子的诱导。染色质免疫沉淀测定表明，SATB2 可直接与 BCL-2、BSP、NANOG、MYC、XIAP、KLF4 和 HOXA2 的启动子结合，表明 SATB2 能够直接调节多能性/自我更新、细胞存活和增殖。由于前列腺 CSC 在癌症起始、进展和转移中起关键作用，我们还研究了 SATB2 敲低对干细胞特性的影响。与对照 scrambled 组相比，SATB2 在前列腺 CSC 中的敲低抑制了球体形成、细胞活力、集落形成、细胞迁移、迁移和侵袭。SATB2 在 CSCs 中的敲低还上调了 E-钙粘蛋白的表达，并抑制了 N-钙粘蛋白、SNAIL、SLUG 和 ZEB1 的表达。SATB2 的表达在前列腺腺癌中明显高于正常组织。总的来说，我们的数据表明，SATB2 作为一种致癌因子，通过诱导 CSC 特性，能够诱导 PrEC 发生恶性变化。
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