iASPP facilitates tumor growth by promoting mTOR-dependent autophagy in human non-small-cell lung cancer

Cell Death & Disease
Yijun XueJinfeng Chen

Abstract

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.

References

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Citations

Aug 21, 2018·The International Journal of Neuroscience·Mei SunHong Cheng
Feb 9, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Milan HanoZdena Sulová
Aug 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Shuo ChenXin Lu
Nov 28, 2019·Therapeutic Advances in Respiratory Disease·Shi-Xia LiaoYao Ou-Yang
Apr 18, 2021·Cellular and Molecular Life Sciences : CMLS·Xue LiHuaiyong Chen
Sep 22, 2021·Cell Biology International·Zijian WangShengjie Yang

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Methods Mentioned

BETA
xenograft
dissecting
xenografts
PCR
fluorescence microscopy
Protein Assay

Software Mentioned

SPSS
PathScan

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