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Leukocyte cell‐derived chemotaxin 2 antagonizes MET receptor activation to suppress hepatocellular carcinoma vascular invasion by protein tyrosine phosphatase 1B recruitment
Author(s) -
Chen ChiKuan,
Yang ChingYao,
Hua KuoTai,
Ho MingChih,
Johansson Gunnar,
Jeng YungMing,
Chen ChiungNien,
Chen MinWei,
Lee WeiJiunn,
Su JenLiang,
Lai TsungChing,
Chou ChiChi,
Ho BingChing,
Chang ChuanFa,
Lee PoHuang,
Chang KingJen,
Hsiao Michael,
Lin MingTsan,
Kuo MinLiang
Publication year - 2014
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.26738
Subject(s) - protein tyrosine phosphatase , hepatocellular carcinoma , cancer research , receptor tyrosine kinase , phosphatase , receptor , microbiology and biotechnology , phosphorylation , biology , biochemistry
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. (H epatology 2014;59:974‐985)