Oncotarget

Research Papers:

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

Tingting Feng, Lin Zheng, Feng Liu, Xiaoying Xu, Sheng Mao, Xiao Wang, Juan Liu, Yi Lu, Weiming Zhao, Xiuping Yu and Wei Tang _

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Oncotarget. 2016; 7:58381-58395. https://doi.org/10.18632/oncotarget.11126

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Abstract

Tingting Feng1,*, Lin Zheng1,4,*, Feng Liu2, Xiaoying Xu1, Sheng Mao1, Xiao Wang3, Juan Liu1, Yi Lu2, Weiming Zhao1, Xiuping Yu1, Wei Tang1

1Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China

2Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, China

3Department of Pathology, Shandong University School of Medicine, Jinan, Shandong, China

4Microbiological Laboratory, The Affiliated Hospital of School of Medicine of Ningbo University, Ningbo, Zhejiang, China

*These authors have contributed equally to this work

Correspondence to:

Wei Tang, email: [email protected]

Keywords: progranulin, mTOR signaling, tumorigenesis, transformation, cervical cancer

Received: December 15, 2015    Accepted: July 26, 2016    Published: August 09, 2016

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.


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