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

Li G; Schaider H; Satyamoorthy KHanakawa YHashimoto KHerlyn M

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

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

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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.

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《Oncogene》 |2001年第56期|8125-8135|共11页
作者
Li G; Schaider H; Satyamoorthy KHanakawa YHashimoto KHerlyn M;
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作者单位

The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania, PA 19104, USA.;

o.cwru.edu;

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原文格式 PDF
正文语种英语
中图分类肿瘤学;
关键词
Autocrine Communication; Cadherins; Hepatocyte Growth Factor; Melanoma; 自身分泌性细胞交流; 钙粘着糖蛋白类; 肝细胞生长因子; 黑色素瘤;

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

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