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  • Title: FAM9C plays an anti-apoptotic role through activation of the PI3K/Akt pathway in human hepatocellular carcinoma.
    Author: Zhou JD, Shen F, Ji JS, Zheng K, Huang M, Wu JC.
    Journal: Oncol Rep; 2013 Sep; 30(3):1275-84. PubMed ID: 23836295.
    Abstract:
    The function of FAM9C encoding a testis-exclusively expressed and nuclear-localized protein remains unknown. In the present study, we evaluated the role of FAM9C in human hepatocellular carcinoma. We found that among three FAM9 family members, only FAM9C was frequently upregulated in HCC specimens compared with that in corresponding adjacent non-cancer liver tissues. FAM9C was located in the nucleus of HCC cells, as shown by both western blotting and immumofluorescence assays. Significantly, FAM9C overexpression promoted proliferation, clonogenicity in an anchorage-dependent manner, in vivo tumorigenicity of YY-8103, and Huh-7 cells. In contrast, FAM9C knockdown suppressed proliferation, anchorage-dependent colony formation and in vivo tumorigenicity of QGY-7703, and BEL-7404 cells. However, FAM9C had no significant effects on cell cycle progression when FAM9C was stably overexpressed in Huh-7 cells or knocked down in BEL-7404 cells. Most importantly, FAM9C regulated activation of Akt and UV-induced apoptosis in HCC cells. FAM9C overexpression increased the phosphorylation levels of Akt and anti-apoptotic ability of Huh-7 cells, whereas endogenous FAM9C knockdown reduced the phosphorylated levels of Akt and anti-apoptotic ability of BEL-7404 cells. Furthermore, the anti-apoptotic function of FAM9C could be prevented when the PI3K-Akt pathway was in a loss-of-function caused by RNA interference against Akt or PI3K inhibitor LY294002 in HCC cells. Taken together, our data demonstrate that FAM9C as a novel cancer testis gene plays an anti-apoptotic role in human hepatocellular carcinoma through activating the PI3K/Akt signaling pathway, and serves as a promising target for HCC therapy.
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