CD317 Promotes the survival of cancer cells through apoptosis-inducing factor.
CD317 Promotes the survival of cancer cells through apoptosis-inducing factor.
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CD317通过凋亡诱导因子促进癌细胞的存活
DOI：
10.1186/s13046-016-0391-2
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发表时间：
2016-07-22
期刊：
影响因子：
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通讯作者：
Wan X
中科院分区：
文献类型：
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作者：
Li X;Zhang G;Chen Q;Lin Y;Li J;Ruan Q;Chen Y;Yu G;Wan X
低营养环境是实体瘤生长的主要障碍。然而，许多肿瘤已经发展出适应性机制来规避对外源性生长因子的需求。本研究采用siRNA干扰或质粒转染技术分别敲低或增强CD 317在哺乳动物癌细胞中的表达，并将这些CD 317操纵的细胞进行血清剥夺，以研究CD 317在应激诱导的细胞凋亡中的作用及其机制。我们报告说，CD 317，先天免疫基因在人类癌症中过表达，保护癌细胞免受血清剥夺诱导的凋亡。在肿瘤细胞中，CD 317的丢失显著增强了其对血清剥夺诱导的细胞凋亡的易感性，而对自噬或半胱天冬酶激活没有影响，表明CD 317功能的自噬和半胱天冬酶独立机制。重要的是，CD 317敲低血清剥夺肿瘤细胞损害线粒体功能，随后促进凋亡诱导因子（AIF）的释放和核转位，但对细胞色素C的线粒体和细胞质分布几乎没有影响，细胞色素C是一种促凋亡因子，从线粒体释放，启动半胱天冬酶处理响应死亡刺激。此外，HEK 293 T细胞中CD 317的过表达抑制血清剥夺诱导的细胞凋亡以及AIF的释放和核积累。我们的数据表明，在营养不良的条件下，CD 317作为一种抗凋亡因子通过AIF轴发挥作用，并可能作为一个潜在的药物靶点用于癌症治疗。本文的在线版本（doi：10.1186/s13046-016-0391-2）包含补充材料，可供授权用户使用。
Low nutrient environment is a major obstacle to solid tumor growth. However, many tumors have developed adaptive mechanisms to circumvent the requirement for exogenous growth factors. Here we used siRNA interference or plasmid transfection techniques to knockdown or enhance CD317 expression respectively, in mammalian cancer cells, and subjected these CD317-manipulated cells to serum deprivation to study the role of CD317 on stress-induced apoptosis and the underlying mechanism. We report that CD317, an innate immune gene overexpressed in human cancers, protected cancer cells against serum deprivation-induced apoptosis. In tumor cells, loss of CD317 markedly enhanced their susceptibility to serum deprivation-induced apoptosis with no effect on autophagy or caspase activation, indicating an autophagy- and caspase-independent mechanism of CD317 function. Importantly, CD317 knockdown in serum-deprived tumor cells impaired mitochondria function and subsequently promoted apoptosis-inducing factor (AIF) release and nuclear translocation but had little effect on mitochondrial and cytoplasmic distributions of cytochrome C, a pro-apoptotic factor released from mitochondria that initiates caspase processing in response to death stimuli. Furthermore, overexpression of CD317 in HEK293T cells inhibits serum deprivation-induced apoptosis as well as the release and nuclear accumulation of AIF. Our data suggest that CD317 functions as an anti-apoptotic factor through the mitochondria-AIF axis in malnourished condition and may serve as a potential drug target for cancer therapy. The online version of this article (doi:10.1186/s13046-016-0391-2) contains supplementary material, which is available to authorized users.