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• W3044904540 abstract "Objective: MST4 has exhibited functions in regulating cell polarity, Golgi apparatus, cell migration, and cancer. Mechanistically, it affects the activity of p-ERK, Hippo-YAP pathway and autophagy. The aim of this study is to further examine the functions of MST4 in hepatocellular carcinoma (HCC) and the underlying mechanism. Methods: The expression level of MST4 in HCC and noncancer adjacent liver tissues was determined by qRT-PCR and immunohistochemistry staining. Wild-type MST4 (MST4) and a dominant-negative mutant of MST4 (dnMST4) were overexpressed in HCC cell lines, respectively. CCK-8 assay, EdU incorporation assay, and soft agar assay were used to determine cell proliferation in vitro. The xenograft mouse model was employed to determine HCC cell growth in vivo. Cell cycle analysis was performed by PI staining and flow cytometry. The expression of key members in PI3K/AKT pathway was detected by Western blot analysis. Results: In our study, we reported new evidence that MST4 was frequently down-regulated in HCC tissues. Gain-of-function and loss-of-function experiments demonstrated that MST4 negatively regulated in vitro HCC cell proliferation. Additionally, MST4 overexpression suppressed Bel-7404 cell tumor growth in nude mice. Further experiments revealed that the growth-inhibitory effect of MST4 overexpression was partly due to a G1-phase cell cycle arrest. Importantly, mechanistic investigations suggested that dnMST4 significantly elevated the phosphorylation levels of key members of PI3K/AKT pathway, and the selective PI3K inhibitor LY294002 can reverse the proliferation-promoting effect of dnMST4. Conclusions: Overall, our results provide a new insight into the clinical significance, functions and molecular mechanism of MST4 in HCC, suggesting that MST4 might have a potential therapeutic value in the HCC clinical treatment." @default.
• W3044904540 created "2020-07-29" @default.
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• W3044904540 date "2020-01-01" @default.
• W3044904540 modified "2023-10-05" @default.
• W3044904540 title "MST4 inhibits human hepatocellular carcinoma cell proliferation and induces cell cycle arrest via suppression of PI3K/AKT pathway" @default.
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• W3044904540 doi "https://doi.org/10.7150/jca.45822" @default.
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