Downregulation of E-cadherin and Desmoglein 1 by autocrine hepatocyte growth factor during melanoma development

Li, Gang, Schaider, Helmut, Satyamoorthy, Kapaettu, Hanakawa, Yasushi, Hashimoto, Koji and Herlyn, Meenhard (2001) Downregulation of E-cadherin and Desmoglein 1 by autocrine hepatocyte growth factor during melanoma development. Oncogene, 20 56: 8125-8135. doi:10.1038/sj.onc.1205034


Author Li, Gang
Schaider, Helmut
Satyamoorthy, Kapaettu
Hanakawa, Yasushi
Hashimoto, Koji
Herlyn, Meenhard
Title Downregulation of E-cadherin and Desmoglein 1 by autocrine hepatocyte growth factor during melanoma development
Journal name Oncogene   Check publisher's open access policy
ISSN 0950-9232
1476-5594
Publication date 2001-12-06
Year available 2001
Sub-type Article (original research)
DOI 10.1038/sj.onc.1205034
Volume 20
Issue 56
Start page 8125
End page 8135
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract During melanoma development, transformed cells evade keratinocyte-mediated control by downregulating cell adhesion molecules. This study investigated the regulation of cell adhesion by hepatocyte growth factor (HGF) in melanoma. Melanocytes and two melanoma lines, WM164 and WM35, expressed normal level E-cadherin and Desmoglein 1, whereas most melanomas (18 out of 20) expressed no E-cadherin and significantly reduced Desmoglein 1. Overexpression of dominant negative E-cadherin and Desmoglein in melanocytes demonstrated that both molecules contribute to adhesion between melanocytes and keratinocytes. In contrast to melanocytes, most melanomas expressed HGF. All melanocytic cells expressed the HGF receptor c-Met, and autocrine HGF caused constitutive activation of c-Met, MAPK and PI3K. When autocrine activation was induced with HGF-expressing adenovirus, E-cadherin and Desmoglein 1 were decreased in melanocytes, WM164 and WM35. MAPK inhibitor PD98059 and PI3K inhibitor wortmannin partially blocked the downregulation, suggesting that both pathways are involved in this process. c-Met was coimmunoprecipitated with E-cadherin, Desmoglein 1 and Plakoglobin, suggesting that they form a complex (es) that acts to regulate intercellular adhesion. Together, the results indicate that autocrine HGF decouples melanomas from keratinocytes by downregulating E-cadherin and Desmoglein 1, therefore frees melanoma cells from the control by keratinocytes and allows dissemination of the tumor mass.
Keyword HGF
Autocrine
E-cadherin
Desmoglein
Melanoma
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Medicine Publications
 
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