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Cited by 212Melanoma and MAPK PathwaysCell Adhesion Molecules ResearchLiver physiology and pathology

The DOI matches its Crossref record; 94 of the 94 references it cites were found in a registry or an index.

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, Herlyn, Meenhard·2001·Oncogene
DOI 10.1038/sj.onc.1205034
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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.

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Crossref · 10.1038/sj.onc.1205034

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Research works printed but not linked: 2

  1. Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, Aaronson SA . 1991a Science 251: 802–804 · DOI
  2. Hsu MY, Wheelock MJ, Johnson KR, Herlyn M . 1996 J. Investig. Dermatol. Symp. Proc. 1: 188–194

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Metadata

Authors
Li, G., Schaider, H., Satyamoorthy, K., Hanakawa, Y., Hashimoto, K., & Herlyn, M.
Affiliations
  • The Wistar Institute (US)
  • Ehime University (JP)
Corresponding author
Herlyn, Meenhard
ORCID
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
2001-12-06
Volume
20
Issue
56
Pages
8125-8135
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
DOI
10.1038/sj.onc.1205034
OpenAlex
W2010980929
Cited by
212
References
94
Citations by year
2025: 2 · 2024: 5 · 2023: 8 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 11 · 2016: 8 · 2015: 11 · 2014: 8 · 2013: 9 · 2012: 9
FWCI
3.15
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Tokyo
  • National Institutes of Health
  • National Cancer Institute (R01CA047159, CA 47159, R01CA080999, CA-10815, CA 76674, CA-25874, R01CA076674, CA80999, P01CA025874, P30CA010815)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
melanoma, hepatocyte growth factor, E-cadherin, desmoglein 1, c-Met, autocrine signaling, cell adhesion, plakoglobin, MAPK signaling, PI3K signaling, metastasis, melanocytes
MeSH terms
Cell Adhesion, Cytoskeletal Proteins, Humans, Melanocytes, Melanoma, Precipitin Tests, RNA, Neoplasm, Tumor Cells, Cultured, Signal Transduction, Down-Regulation, Keratinocytes, Cadherins, Hepatocyte Growth Factor, Proto-Oncogene Proteins c-met, Phosphatidylinositol 3-Kinases, Autocrine Communication, Mitogen-Activated Protein Kinases, Desmoplakins, Desmogleins, Desmoglein 1, gamma Catenin

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