TY - JOUR
T1 - IASPP facilitates tumor growth by promoting mtor-dependent autophagy in human non-small-cell lung cancer
AU - Xue, Yijun
AU - Han, Haibo
AU - Wu, Lina
AU - Pan, Bo
AU - Dong, Bin
AU - Yin, C. Cameron
AU - Tian, Zhihua
AU - Liu, Xijuan
AU - Yang, Yue
AU - Zhang, Hong
AU - Chen, Yingyu
AU - Chen, Jinfeng
N1 - Publisher Copyright:
© The Author(s) 2017.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85041642844&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041642844&partnerID=8YFLogxK
U2 - 10.1038/cddis.2017.515
DO - 10.1038/cddis.2017.515
M3 - Article
C2 - 29072696
AN - SCOPUS:85041642844
SN - 2041-4889
VL - 8
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 10
M1 - e3150
ER -