Bax is necessary for PGC1α pro-apoptotic effect in colorectal cancer cells
Bax is necessary for PGC1α pro-apoptotic effect in colorectal cancer cells
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DOI：
10.4161/cc.10.17.16791
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发表时间：
2011-09-01
期刊：
影响因子：
4.3
通讯作者：
Moschetta, Antonio
中科院分区：
文献类型：
--
作者：
D'Errico, Ilenia;Lo Sasso, Giuseppe;Moschetta, Antonio
我们最近发现，转录共激活因子 PGC1 α（线粒体生物合成和功能的主要调节因子）参与肠上皮细胞命运的控制。此外，PGC1 α 通过促进 ROS 积累以及线粒体介导的细胞凋亡来防止结肠癌形成。在这里，我们对 PGC1 α 的肿瘤抑制活性提供了额外的机制见解，表明其促凋亡作用是由 Bax 介导的。事实上，HCT116 Bax(-/-) 结直肠癌细胞中 PGC1 α 的过度表达会刺激线粒体的产生和活性，但在异种移植模型中它不能诱导细胞死亡，也不能阻止肿瘤生长。 Bax(-/-)细胞中ROS积累的缺乏强化了我们的观点，即PGC1α诱导的氧化爆发是结直肠癌细胞中主要的凋亡驱动因素之一。
We have recently shown that the transcriptional coactivator PGC1 alpha, a master regulator of mitochondrial biogenesis and function, is involved in the control of the intestinal epithelium cell fate. Furthermore, PGC1 alpha protects against colon cancer formation by promoting ROS accumulation and, consequently, mitochondria-mediated apoptosis. Here we provide an additional mechanistic insight into the tumor suppressor activity of PGC1 alpha showing that its pro- apoptotic effect is mediated by Bax. In fact, PGC1 alpha overexpression in HCT116 Bax(-/-) colorectal cancer cells stimulates mitochondrial production and activity, but it fails to induce cell death as well as to oppose tumor growth in the xenograft model. The lack of ROS accumulation in the Bax(-/-) cells strengthens our view that the PGC1 alpha-induced oxidative burst represents one of the main apoptosis-driving factors in colorectal cancer cells.