title: Leukocyte cell-derived chemotaxin 2 antagonizes MET receptor activation to suppress hepatocellular carcinoma vascular invasion by protein tyrosine phosphatase 1B recruitment.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chi-Kuan
authors.initials: CK
authors.lastname: Chen
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Yang
authors.forename: Kuo-Tai
authors.initials: KT
authors.lastname: Hua
authors.forename: Kuo-Ti
authors.initials: KT
authors.lastname: Hua
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Ho
authors.forename: Gunnar
authors.initials: G
authors.lastname: Johansson
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Chiung-Nien
authors.initials: CN
authors.lastname: Chen
authors.forename: Min-Wei
authors.initials: MW
authors.lastname: Chen
authors.forename: Wei-Jiunn
authors.initials: WJ
authors.lastname: Lee
authors.forename: Jen-Liang
authors.initials: JL
authors.lastname: Su
authors.forename: Tsung-Ching
authors.initials: TC
authors.lastname: Lai
authors.forename: Chi-Chi
authors.initials: CC
authors.lastname: Chou
authors.forename: Bing-Ching
authors.initials: BC
authors.lastname: Ho
authors.forename: Chuan-Fa
authors.initials: CF
authors.lastname: Chang
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Lee
authors.forename: King-Jen
authors.initials: KJ
authors.lastname: Chang
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.forename: Ming-Tsan
authors.initials: MT
authors.lastname: Lin
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D056945:Hep G2 Cells; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000737:chemistry / Q000378:metabolism*
chemical_list: C066855:HGF protein, human; D036341:Intercellular Signaling Peptides and Proteins; C103468:LECT2 protein, human; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1