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Hepatocyte growth factor induces Wnt-independent nuclear translocation of beta-catenin after Met-beta-catenin dissociation in hepatocytes.
Cancer Res. 2002 Apr 01; 62(7):2064-71.CR

Abstract

Hepatocyte growth factor (HGF) and Wnt signaling pathways have been shown to be important in embryogenesis and carcinogenesis. The aim of this study was to elucidate the mechanism of functional similarities observed in the two pathways. We used normal rat liver, primary hepatocyte cultures and a dominant-negative Met expression system to study the effect of HGF on Wnt pathway components. We demonstrate novel association of beta-catenin and Met, a tyrosine kinase receptor of HGF, at the inner surface of the hepatocyte membrane. HGF induces dose-dependent nuclear translocation of beta-catenin in primary hepatocyte cultures that is Wnt independent. The source of beta-catenin for translocation in hepatocytes is the Met-beta-catenin complex, which appears to be independent of the E-cadherin-beta-catenin complex. To test the functionality of this association, we used a dominant-negative Met expression system that expresses only the extracellular and transmembrane regions of the beta-subunit of Met. A loss of Met-beta-catenin association resulted in abrogation of nuclear translocation of beta-catenin upon HGF stimulation. This event is tyrosine phosphorylation dependent, and the association of Met and beta-catenin is crucial for this event. We conclude that the HGF causes similar redistribution of beta-catenin as Wnt-1 in the hepatocytes and that this effect is attributable to subcellular association of Met and beta-catenin. The intracellular kinase domain of Met is essential for tyrosine phosphorylation and nuclear translocation of beta-catenin. Part of the multifunctionality of HGF might be attributable to nuclear beta-catenin and the resulting target gene expression.

Authors+Show Affiliations

Division of Cellular and Molecular Pathology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15261, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11929826

Citation

Monga, Satdarshan P S., et al. "Hepatocyte Growth Factor Induces Wnt-independent Nuclear Translocation of Beta-catenin After Met-beta-catenin Dissociation in Hepatocytes." Cancer Research, vol. 62, no. 7, 2002, pp. 2064-71.
Monga SP, Mars WM, Pediaditakis P, et al. Hepatocyte growth factor induces Wnt-independent nuclear translocation of beta-catenin after Met-beta-catenin dissociation in hepatocytes. Cancer Res. 2002;62(7):2064-71.
Monga, S. P., Mars, W. M., Pediaditakis, P., Bell, A., Mulé, K., Bowen, W. C., Wang, X., Zarnegar, R., & Michalopoulos, G. K. (2002). Hepatocyte growth factor induces Wnt-independent nuclear translocation of beta-catenin after Met-beta-catenin dissociation in hepatocytes. Cancer Research, 62(7), 2064-71.
Monga SP, et al. Hepatocyte Growth Factor Induces Wnt-independent Nuclear Translocation of Beta-catenin After Met-beta-catenin Dissociation in Hepatocytes. Cancer Res. 2002 Apr 1;62(7):2064-71. PubMed PMID: 11929826.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatocyte growth factor induces Wnt-independent nuclear translocation of beta-catenin after Met-beta-catenin dissociation in hepatocytes. AU - Monga,Satdarshan P S, AU - Mars,Wendy M, AU - Pediaditakis,Peter, AU - Bell,Aaron, AU - Mulé,Karen, AU - Bowen,William C, AU - Wang,Xue, AU - Zarnegar,Reza, AU - Michalopoulos,George K, PY - 2002/4/4/pubmed PY - 2002/5/8/medline PY - 2002/4/4/entrez SP - 2064 EP - 71 JF - Cancer research JO - Cancer Res. VL - 62 IS - 7 N2 - Hepatocyte growth factor (HGF) and Wnt signaling pathways have been shown to be important in embryogenesis and carcinogenesis. The aim of this study was to elucidate the mechanism of functional similarities observed in the two pathways. We used normal rat liver, primary hepatocyte cultures and a dominant-negative Met expression system to study the effect of HGF on Wnt pathway components. We demonstrate novel association of beta-catenin and Met, a tyrosine kinase receptor of HGF, at the inner surface of the hepatocyte membrane. HGF induces dose-dependent nuclear translocation of beta-catenin in primary hepatocyte cultures that is Wnt independent. The source of beta-catenin for translocation in hepatocytes is the Met-beta-catenin complex, which appears to be independent of the E-cadherin-beta-catenin complex. To test the functionality of this association, we used a dominant-negative Met expression system that expresses only the extracellular and transmembrane regions of the beta-subunit of Met. A loss of Met-beta-catenin association resulted in abrogation of nuclear translocation of beta-catenin upon HGF stimulation. This event is tyrosine phosphorylation dependent, and the association of Met and beta-catenin is crucial for this event. We conclude that the HGF causes similar redistribution of beta-catenin as Wnt-1 in the hepatocytes and that this effect is attributable to subcellular association of Met and beta-catenin. The intracellular kinase domain of Met is essential for tyrosine phosphorylation and nuclear translocation of beta-catenin. Part of the multifunctionality of HGF might be attributable to nuclear beta-catenin and the resulting target gene expression. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11929826/Hepatocyte_growth_factor_induces_Wnt_independent_nuclear_translocation_of_beta_catenin_after_Met_beta_catenin_dissociation_in_hepatocytes_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11929826 DB - PRIME DP - Unbound Medicine ER -