Growth factor progranulin promotes tumorigenesis of cervical cancer via PI3K/Akt/mTOR signaling pathway.

Abstract	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.
Authors	Tingting Feng, Lin Zheng, Feng Liu, Xiaoying Xu, Sheng Mao, Xiao Wang, Juan Liu, Yi Lu, Weiming Zhao, Xiuping Yu, Wei Tang
Journal	Oncotarget (Oncotarget) Vol. 7 Issue 36 Pg. 58381-58395 (09 06 2016) ISSN: 1949-2553 [Electronic] United States
PMID	27517315 (Publication Type: Journal Article)
Chemical References	GRN protein, human Intercellular Signaling Peptides and Proteins Progranulins RNA, Small Interfering MTOR protein, human AKT1 protein, human Proto-Oncogene Proteins c-akt TOR Serine-Threonine Kinases Sirolimus
Topics	Animals Anoikis Carcinogenesis Cell Movement Cell Proliferation Cervix Uteri (metabolism) Female HeLa Cells Humans Intercellular Signaling Peptides and Proteins (metabolism) Mice Mice, Inbred BALB C Mice, Nude Neoplasm Transplantation Phosphatidylinositol 3-Kinases (metabolism) Phosphorylation Progranulins Proto-Oncogene Proteins c-akt (metabolism) RNA, Small Interfering (metabolism) Signal Transduction Sirolimus (chemistry) TOR Serine-Threonine Kinases (metabolism) Uterine Cervical Neoplasms (metabolism, pathology)

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