4.5 Article

TM4SF1, a binding protein of DVL2 in hepatocellular carcinoma, positively regulates beta-catenin/TCF signalling

期刊

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 25, 期 5, 页码 2356-2364

出版社

WILEY
DOI: 10.1111/jcmm.14787

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hepatocellular carcinoma; migration and metastasis; TM4SF1; Wnt; beta-catenin cascade

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The study reveals that TM4SF1 interacts with DVL2 to positively regulate Wnt/beta-catenin signaling, promoting growth and motility of HCC cells. TM4SF1 is upregulated in HCC and induced by Kras signaling, suggesting it may have oncogenic functions in HCC progression and could be a potential target for treatment.
The interaction between Axin and DVL2 is critical for the breaking down of the beta-catenin destruction complex and the activation of the Wnt/beta-catenin cascade. However, this biological process remains poorly understood. In the present study, TM4SF1 was identified as the interacting partner of DVL2 and positively regulated as Wnt/beta-catenin signalling by strengthening the DVL2-Axin interaction. The expression levels of TM4SF1 were elevated in hepatocellular carcinoma (HCC) and were induced by Kras signalling. The overexpression of TM4SF1 promoted the growth and motility of HCC cells, and up-regulated the target genes (Axin2 and cyclin D1). The down-regulation of TM4SF1 impaired the capability of HCC cells for growth, migration and metastasis. In addition, the down-regulation of TM4SF1 promoted the ubiquitination of beta-catenin. In summary, these results reveal the oncogenic functions of TM4SF1 in HCC progression and suggest that TM4SF1 might be a target for treatment.

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