Department of Life Science and Institute of Biotechnology, National Tsing-Hua University, HsinChu, 300, Taiwan (R.O.C.).
Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, 112, Taiwan (R.O.C.).
Sci Rep. 2018 Dec 3;8(1):17550. doi: 10.1038/s41598-018-35592-0.
Endometrial carcinoma is a cancer derived from oncogenesis of the regenerating uterine cavity, in which cytokine stimulation shapes cell differentiation and tissue remodeling. Expression of the stem cell factors SOX2, OCT4, NANOG, and MYC has been linked to tumor malignancy in several cancers. However, how these stem cell factors crosstalk with cytokine signaling to promote malignancy in endometrial carcinoma is still elusive. Here we report that the expression of SOX2 and MYC, but not that of OCT4 and NANOG, correlate with poor histological differentiation and prognosis, while SOX2 expression is negatively associated with MYC level. We found that SOX2-high endometrial carcinoma cells possessed a higher colony-forming ability than their SOX2-low counterparts, and knockdown of SOX2 attenuated the colony-forming ability. We observed that SOX2 regulated EGFR expression in a SOX2-EGFR positive feedback loop. EGF stimulation induced SOX2 expression and promoted migration of endometrial carcinoma cells, whereas TGF-β stimulation inhibited SOX2 expression and attenuated the colony-forming ability. Immunohistochemistry analysis revealed that SOX2 expression correlated with lymph node infiltration of endometrial carcinoma. Our findings support that cytokine-induced stem cell factor SOX2 possesses oncogenic properties, with the potential to serve as a prognostic biomarker in endometrial carcinoma.
子宫内膜癌是一种起源于再生子宫腔的肿瘤发生的癌症，其中细胞因子刺激塑造了细胞分化和组织重塑。在几种癌症中，干细胞因子 SOX2、OCT4、NANOG 和 MYC 的表达与肿瘤恶性程度有关。然而，这些干细胞因子如何与细胞因子信号转导相互作用以促进子宫内膜癌的恶性程度仍然难以捉摸。在这里，我们报告 SOX2 和 MYC 的表达与组织学分化不良和预后不良相关，而不是 OCT4 和 NANOG 的表达，而 SOX2 的表达与 MYC 水平呈负相关。我们发现 SOX2-高子宫内膜癌细胞比 SOX2-低的细胞具有更高的集落形成能力，而 SOX2 的敲低则减弱了集落形成能力。我们观察到 SOX2 在 SOX2-EGFR 正反馈环中调节 EGFR 的表达。EGF 刺激诱导 SOX2 的表达并促进子宫内膜癌细胞的迁移，而 TGF-β 刺激抑制 SOX2 的表达并减弱集落形成能力。免疫组织化学分析显示 SOX2 的表达与子宫内膜癌的淋巴结浸润相关。我们的研究结果支持细胞因子诱导的干细胞因子 SOX2 具有致癌特性，并有可能成为子宫内膜癌的预后生物标志物。
