title: 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: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Tingting
authors: T
authors: Feng
authors: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.|Microbiological Laboratory, The Affiliated Hospital of School of Medicine of Ningbo University, Ningbo, Zhejiang, China.
authors: Lin
authors: L
authors: Zheng
authors: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Feng
authors: F
authors: Liu
authors: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Xiaoying
authors: X
authors: Xu
authors: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Sheng
authors: S
authors: Mao
authors: Department of Pathology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Xiao
authors: X
authors: Wang
authors: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Juan
authors: J
authors: Liu
authors: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Yi
authors: Y
authors: Lu
authors: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Weiming
authors: W
authors: Zhao
authors: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Xiuping
authors: X
authors: Yu
authors: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Wei
authors: W
authors: Tang
mesh_terms: D000818:Animals; D023102:Anoikis; D063646:Carcinogenesis; D002465:Cell Movement; D049109:Cell Proliferation; D002584:Cervix Uteri / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D000077153:Progranulins; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000737:chemistry; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D000077153:Progranulins; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C492314:GRN protein, human; C546842:MTOR protein, human; C494918:AKT1 protein, human
keywords: cervical cancer; mTOR signaling; progranulin; transformation; tumorigenesis