iASPP facilitates tumor growth by promoting mTOR-dependent autophagy in human non-small-cell lung cancer.
iASPP facilitates tumor growth by promoting mTOR-dependent autophagy in human non-small-cell lung cancer.
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iASPP 通过促进人类非小细胞肺癌中 mTOR 依赖性自噬促进肿瘤生长
DOI：
10.1038/cddis.2017.515
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发表时间：
2017-10-26
影响因子：
9
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Xue Y;Han H;Wu L;Pan B;Dong B;Yin CC;Tian Z;Liu X;Yang Y;Zhang H;Chen Y;Chen J
自噬在癌症的发病机制、治疗反应和临床结果中起关键作用。虽然最近的一份报告显示了iASPP在抑制自噬中的作用，但其作为自噬调节剂的潜在活性尚未在肺癌中研究。本研究旨在探讨iASPP在人非小细胞肺癌中介导自噬的潜在功能及其分子机制。我们的数据表明，在体外自噬体形成阶段，iASPP的强制表达触发自噬通量，而iASPP的抑制抑制自噬。此外，iASPP在SCID/NOD小鼠中的体内过表达促进了肿瘤发生和自噬，增加了从LC 3-I到LC 3-II的转化。iASPP的作用是通过激活mTOR通路介导的。最后，细胞质iASPP表达在肺癌患者中上调，并被鉴定为患者样本中肺癌特异性死亡的独立预后不良因素。综上所述，我们的数据表明，iASPP可以通过增加自噬流量来促进肿瘤生长，并且iASPP可以作为肺癌的不良预后因子和潜在的治疗靶点。
Autophagy serves a critical function in the pathogenesis, response to therapy and clinical outcome in cancers. Although a recent report showed a role of iASPP in suppressing autophagy, its potential activity as a regulator of autophagy has not been investigated in lung cancer. Here we investigated the potential function and molecular mechanism of iASPP in mediating autophagy in human non-small-cell lung cancer. Our data suggested that forced expression of iASPP triggered autophagic flux, while inhibition of iASPP suppressed autophagy at the autophagsome formation stage in vitro. Furthermore, in vivo overexpression of iASPP in SCID/NOD mice promoted tumorigenesis and autophagy, with an increase in the conversion from LC3-I to LC3-II. The effects of iASPP were mediated through activation of mTOR pathway. Finally, cytoplasmic iASPP expression was upregulated in lung cancer patients, and was identified as an independent poor prognostic factor for lung cancer-specific death in patient samples. Taken together, our data showed that iASPP could promote tumor growth by increasing autophagic flux, and iASPP could serve as a poor prognostic factor and a potential therapeutic target in lung cancer.
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影响因子：
3.8
作者：
Chen J;Xie F;Zhang L;Jiang WG
通讯作者：
Jiang WG
影响因子：
8
作者：
Rebecca VW;Amaravadi RK
通讯作者：
Amaravadi RK
人肺腺癌细胞获得性顺铂耐药与自噬增强相关
影响因子：
3.4
作者：
Ren, Jing-Hua;He, Wen-Shan;Wu, Gang
通讯作者：
Wu, Gang
影响因子：
3.7
作者：
Laska, Magdalena J.;Strandbygard, Dorthe;Nexo, Bjorn A.
通讯作者：
Nexo, Bjorn A.
影响因子：
11.5
作者：
Jiang, LiLi;Siu, Michelle K. Y.;Cheung, Annie N. Y.
通讯作者：
Cheung, Annie N. Y.