Regulation of β-catenin transcription activity by leupaxin in hepatocellular carcinoma
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In human cancers, β-catenin is accumulated in the nucleus and activates mRNA transcription of many oncogenic genes, such as cyclin D1 and c-myc. However, the mechanism of β-catenin-mediated transcriptional activation remains largely unknown. In the present study, we identified leupaxin, an adaptor protein sharing homology with the focal adhesion protein, as a novel coactivator for β-catenin in human hepatocellular carcinoma (HCC). We show that leupaxin could interact with β-catenin and enhance its transcriptional activity through recruitment of coactivator complex, including steroid receptor coactivator 1 (SRC-1) and P300. As a result, leupaxin regulates HCC cell proliferation and cell-cycle progression in the presence of intact Wnt/β-catenin signaling. Furthermore, leupaxin is overexpressed in HCC tissues and correlated with mRNA levels of cyclin D1 and c-myc. Therefore, this is the first demonstration of a role for the leupaxin in the regulation of HCC progression, at least in part, by enhancing β-catenin transcription activity.
KeywordsHepatocellular carcinoma (HCC) Leupaxin β-catenin Coactivator Transcription activity
This work was supported by the National Natural Science Foundation, People’s Republic of China, grant no. 31401185 (to Dr. Bin Liu) and no. 81402478 (to Dr. Zhi-Xiang Wu).
Conflicts of interest
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