Cancer stem-like cells can be induced through dedifferentiation under hypoxic conditions in glioma, hepatoma and lung cancer.
Cancer stem-like cells can be induced through dedifferentiation under hypoxic conditions in glioma, hepatoma and lung cancer.
复制标题
神经胶质瘤、肝癌和肺癌在缺氧条件下可以通过去分化诱导癌症干细胞样细胞
DOI：
10.1038/cddiscovery.2016.105
复制
发表时间：
2017
影响因子：
7
通讯作者：
Wu N
中科院分区：
文献类型：
--
作者：
Wang P;Wan WW;Xiong SL;Feng H;Wu N
传统研究表明，转录因子包括SOX-2、OCT-4、KLF-4、Nanog和Lin-28A参与正常组织的去分化和重编程过程。缺氧是肿瘤中存在的一种生理现象，可促进SOX-2、OCT-4、KLF-4、Nanog和Lin-28A的表达。因此，一个有趣的问题是，缺氧是否作为一种刺激因素促进去分化过程并诱导癌症干细胞样细胞的形成。研究表明，OCT-4和Nanog过表达在肺腺癌中通过去分化诱导癌症干细胞样细胞的形成并增强恶性，而胰腺癌细胞中SOX-2的重编程也促进了去分化过程。因此，我们在胶质瘤、肺癌和肝癌细胞中对这一现象进行了研究，发现上述转录因子在缺氧条件下高表达并诱导球的形成，表现为不对称分裂和细胞周期阻滞。缺氧诱导的去分化过程凸显了癌症发展和复发的新模式，表明在开发肿瘤治疗时应考虑各种癌细胞和缺氧微环境。
Traditional studies have shown that transcription factors, including SOX-2, OCT-4, KLF-4, Nanog and Lin-28A, contribute to the dedifferentiation and reprogramming process in normal tissues. Hypoxia is a physiological phenomenon that exists in tumors and promotes the expression of SOX-2, OCT-4, KLF-4, Nanog and Lin-28A. Therefore, an interesting question is whether hypoxia as a stimulating factor promotes the process of dedifferentiation and induces the formation of cancer stem-like cells. Studies have shown that OCT-4 and Nanog overexpression induced the formation of cancer stem cell-like cells through dedifferentiation and enhanced malignancy in lung adenocarcinoma, and reprogramming SOX-2 in pancreatic cancer cells also promoted the dedifferentiation process. Therefore, we investigated this phenomenon in glioma, lung cancer and hepatoma cells and found that the transcription factors mentioned above were highly expressed under hypoxic conditions and induced the formation of spheres, which exhibited asymmetric division and cell cycle arrest. The dedifferentiation process induced by hypoxia highlights a new pattern of cancer development and recurrence, demonstrating that all kinds of cancer cells and the hypoxic microenvironment should be taken into consideration when developing tumor therapies.