Open AccessGrowth factor progranulin promotes tumorigenesis of cervical cancer via PI3K/Akt/mTOR signaling pathway
Author(s) -
Tingting Feng,
Lin Zheng,
Feng Liu,
Xiaoying Xu,
Sheng Mao,
Xiao Wang,
Juan Liu,
Yi Lü,
Weiming Zhao,
Xiuping Yu,
Wei Tang
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.11126
Subject(s) - pi3k/akt/mtor pathway , rptor , carcinogenesis , cancer research , protein kinase b , autocrine signalling , signal transduction , mtorc2 , medicine , cancer , biology , microbiology and biotechnology , mtorc1 , receptor
Progranulin (PGRN) is an autocrine growth factor with tumorigenic roles in various tumors including cervical cancer. In this study, we investigated mammalian target of rapamycin (mTOR) signaling in response to PGRN induction and the contribution of the PGRN-stimulated PI3K/Akt/mTOR signaling pathway in the transformation and progression of cervical cancer. Here we identified a strong linkage between PGRN and phosphorylated-mTOR in cervical cancer tissues. PGRN promoted the phosphorylation of mTOR and activated mTOR signaling in human cervical mucosa epithelial cells and cervical cancer cells, and TNFR2 was needed for PGRN-stimulated mTOR signaling. Inhibition of mTOR signaling with rapamycin decreased PGRN-stimulated protein synthesis, transformation and proliferation of cervical cells in vitro, and tumor formation and growth in vivo. Thus, our findings update the signal transduction pathways of PGRN by suggesting that mTOR signaling contributes to PGRN-stimulated carcinogenesis of cervical cancer. Inhibition of PGRN/PI3K/Akt/mTOR signaling may be targeted in treatment of cervical cancer.