Autophagy plays an important role in sternness mediation and the novel dual function of EIG121 in both autophagy and sternness regulation of endometrial carcinoma JEC cells
Autophagy plays an important role in sternness mediation and the novel dual function of EIG121 in both autophagy and sternness regulation of endometrial carcinoma JEC cells
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DOI：
10.3892/ijo.2017.4047
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发表时间：
2017-08-01
影响因子：
5.2
通讯作者：
Zhang, Keqiang
中科院分区：
文献类型：
--
作者：
Ran, Xiaomin;Zhou, Ping;Zhang, Keqiang
子宫内膜癌（EC）是世界上第三大常见的妇科恶性肿瘤，并且被认为是化疗不良反应的癌症。化疗耐药的机制有两种：肿瘤干细胞的干细胞性和促生存自噬的激活。研究发现，自噬是肿瘤干细胞存活、多药耐药以及维持肿瘤干细胞与正常癌细胞稳态的主要因素之一。然而，CSCs与EC细胞自噬的关系尚不清楚。在这项研究中，在子宫内膜癌干细胞（ECSC）中发现了更高的自噬水平，并且在连续培养的JEC球体中，干细胞与自噬保持一致。自噬抑制降低了JEC球中CSCs的特性，并增强了ECSCs对紫杉醇的敏感性。此外，发现EIG121不仅在正常JEC细胞中，而且在JEC获得的CSC中，在自噬和干细胞化的调节中发挥双重功能。这些发现可能有助于开发子宫内膜癌的靶向治疗。
Endometrial cancer (EC) is the third most common gynecologic malignancy in the world, and is considered a chemotherapy poor responding cancer. There are two underlying mechanisms on chemoresistance: the sternness of cancer stem cells (CSCs) and activation of pro-survival autophagy. It was found that autophagy is one of the main factors of cancer stem cell survival, multidrug resistance and maintenance of the homeostasis of cancer stem cells and normal cancer cells. However, the relationship between CSCs and autophagy of EC cells is still unknown. In this study, higher autophagy level was found in endometrial cancer stem cells (ECSCs) and sternness kept in line with autophagy in successive cultured JEC spheres. Autophagy inhibition decreased the properties of CSCs in JEC spheres and enhanced sensitivity of ECSCs to paclitaxel. Besides, it was found that EIG121 exerted dual functions in the regulation of autophagy and sternness not only in normal JEC cells but also JEC obtained CSCs. These findings could be useful for developing targeted therapies for endometrial carcinoma.