Leukocyte cell-derived chemotaxin 2 antagonizes MET receptor activation to suppress hepatocellular carcinoma vascular invasion by protein tyrosine phosphatase 1B recruitment

Chi Kuan Chen, Ching Yao Yang, Kuo Tai Hua, Ming Chih Ho, Gunnar Johansson, Yung Ming Jeng, Chiung Nien Chen, Min Wei Chen, Wei Jiunn Lee, Jen Liang Su, Tsung Ching Lai, Chi Chi Chou, Bing Ching Ho, Chuan Fa Chang, Po Huang Lee, King Jen Chang, Michael Hsiao, Ming Tsan Lin, Min Liang Kuo

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28 Citations (Scopus)

Abstract

Leukocyte cell-derived chemotoxin 2 (LECT2) has been shown to act as a tumor suppressor in hepatocellular carcinoma (HCC). However, the underlying mechanism has not yet been completely defined. Here, we employ a LECT2-affinity column plus liquid chromatography coupled with tandem mass spectrometry to identify LECT2-binding proteins and found that MET receptor strongly interacted with LECT2 protein. Despite the presence of hepatocyte growth factor, the LECT2 binding causes an antagonistic effect to MET receptor activation through recruitment of protein tyrosine phosphatase 1B. The antagonistic effect of LECT2 on MET activation also mainly contributes to the blockage of vascular invasion and metastasis of HCC. Furthermore, serial deletions and mutations of LECT2 showed that the HxGxD motif is primarily responsible for MET receptor binding and its antagonistic effects. Conclusion: These findings reveal a novel, specific inhibitory function of LECT2 in HCC by the direct binding and inactivation of MET, opening a potential avenue for treating MET-related liver cancer. (Hepatology 2014;59:974-985).

Original languageEnglish
Pages (from-to)974-985
Number of pages12
JournalHepatology
Volume59
Issue number3
DOIs
Publication statusPublished - Mar 2014

ASJC Scopus subject areas

  • Hepatology

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    Chen, C. K., Yang, C. Y., Hua, K. T., Ho, M. C., Johansson, G., Jeng, Y. M., Chen, C. N., Chen, M. W., Lee, W. J., Su, J. L., Lai, T. C., Chou, C. C., Ho, B. C., Chang, C. F., Lee, P. H., Chang, K. J., Hsiao, M., Lin, M. T., & Kuo, M. L. (2014). Leukocyte cell-derived chemotaxin 2 antagonizes MET receptor activation to suppress hepatocellular carcinoma vascular invasion by protein tyrosine phosphatase 1B recruitment. Hepatology, 59(3), 974-985. https://doi.org/10.1002/hep.26738