An inflammatory-CCRK circuitry in obesity-associated hepatocarcinogenesis
Refereed conference paper presented and published in conference proceedings

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AbstractObesity increases the risk of hepatocellular carcinoma (HCC) especially in men. We have previously shown that cell cycle-related kinase (CCRK) is an androgen receptor (AR)-driven oncogene contributing to male predominance of HCC. Here, we show that CCRK collaborates with obesity-induced signaling to promote non-alcoholic steatohepatitis (NASH)-related hepatocarcinogenesis. Ccrk ablation in liver of male obese mice not only abrogated lipid accumulation, glucose intolerance and insulin resistance, but also HCC development. Mechanistically, CCRK fueled a feedforward loop via STAT3-AR signaling, which activated mTORC1 cascade via GSK3β phosphorylation. Hepatic CCRK induction in transgenic mice stimulated mTORC1-dependent G-csf expression to enhance myeloid-derived suppressor cell recruitment and tumorigenicity. As we also showed STAT3-AR-CCRK-mTORC1 activation in human NASH-HCCs, our findings unveil the dual roles of an inflammatory-CCRK circuitry in driving metabolic and immunosuppressive reprogramming through mTORC1, thereby establishing a pro-tumorigenic microenvironment for obesity-associated HCC development. Acknowledgement: This work is supported by the RGC
All Author(s) ListAlfred S.L. CHENG, Hanyong SUN, Weiqin YANG, Yuan TIAN, Xuezhen ZENG, Jingying ZHOU, Myth T.S. MOK, Yu FENG, Liangliang XU, Shun-Wa TSANG, King-Lau CHOW, Grace L.H. WONG, Vincent W.S. WONG
Name of ConferenceThe 77th Annual Meeting of the Japanese Cancer Association
Start Date of Conference27/09/2018
End Date of Conference29/09/2018
Place of ConferenceOsaka
Country/Region of ConferenceJapan
LanguagesEnglish-United Kingdom

Last updated on 2019-02-12 at 15:54