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- W4361949497 abstract "<div>Abstract<p><b>Purpose:</b> Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is overexpressed in many types of cancer. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in hepatocellular carcinoma (HCC).</p><p><b>Experimental Design:</b> MAP4K4 expression was examined in 20 fresh HCCs and corresponding nontumor liver tissues. Immunohistochemistry for MAP4K4 was performed on additional 400 HCCs, of which 305 (76%) were positive for hepatitis B surface antigens. The clinical significance of MAP4K4 expression was analyzed. MAP4K4 downregulation was performed in HCC cell lines HepG2 and Hep3B with high abundance of MAP4K4, and the effects of <i>MAP4K4</i> silencing on cell proliferation <i>in vitro</i> and tumor growth <i>in vivo</i> were evaluated. Quantitative real-time PCR arrays were employed to identify the MAP4K4-regulated signaling pathways.</p><p><b>Results:</b> MAP4K4 was aberrantly overexpressed in HCCs relative to adjacent nontumor liver tissues. This overexpression was significantly associated with larger tumor size, increased histologic grade, advanced tumor stage, and intrahepatic metastasis, as well as worse overall survival and higher early recurrence rate. Knockdown of the <i>MAP4K4</i> expression reduced cell proliferation, blocked cell cycle at S phase, and increased apoptosis. The antitumor effects of MAP4K4 silencing were also observed <i>in vivo</i>, manifested as retarded tumor xenograft growth. Furthermore, multiple tumor progression–related signaling pathways including JNK, NFκB, and toll-like receptors were repressed by MAP4K4 downregulation.</p><p><b>Conclusions:</b> MAP4K4 overexpression is an independent predictor of poor prognosis of HCC patients, and inhibition of its expression might be of therapeutic significance. <i>Clin Cancer Res; 17(4); 1–11. ©2010 AACR</i>.</p></div>" @default.
- W4361949497 created "2023-04-05" @default.
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- W4361949497 date "2023-03-31" @default.
- W4361949497 modified "2023-09-25" @default.
- W4361949497 title "Data from ShRNA-Targeted MAP4K4 Inhibits Hepatocellular Carcinoma Growth" @default.
- W4361949497 doi "https://doi.org/10.1158/1078-0432.c.6518188.v1" @default.
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