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首页> 外文期刊>Cell cycle >Bax is necessary for PGC1alpha pro-apoptotic effect in colorectal cancer cells.
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Bax is necessary for PGC1alpha pro-apoptotic effect in colorectal cancer cells.

机译:Bax对于PGC1alpha在大肠癌细胞中的促凋亡作用是必需的。

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摘要

We have recently shown that the transcriptional coactivator PGC1alpha, a master regulator of mitochondrial biogenesis and function, is involved in the control of the intestinal epithelium cell fate. Furthermore, PGC1alpha 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 PGC1alpha showing that its pro-apoptotic effect is mediated by Bax. In fact, PGC1alpha 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 PGC1alpha-induced oxidative burst represents one of the main apoptosis-driving factors in colorectal cancer cells.
机译:我们最近表明,转录共激活因子PGC1alpha,线粒体生物发生和功能的主要调节剂,参与肠上皮细胞命运的控制。此外,PGC1alpha通过促进ROS积累,从而促进线粒体介导的细胞凋亡,防止结肠癌的形成。在这里,我们提供了对PGC1alpha的抑癌活性的另一种机制的见解,表明其促凋亡作用是由Bax介导的。事实上,PGC1alpha在HCT116 Bax(-/-)结直肠癌细胞中的过度表达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并反对肿瘤的生长。 Bax(-/-)细胞中ROS的缺乏增强了我们的观点,即PGC1alpha诱导的氧化爆发代表大肠癌细胞中主要的凋亡驱动因子之一。

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