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
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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“Given the ability of melanoma cells to promote growth and invasion through the secretion of protumorigenic factors (11–13), it is plausible that beyond cancer cell–intrinsic mechanisms, phenotype plasticity and ferroptosis vulnerability of drug-resistant clones may involve autocrine or paracrine circuits.”
From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [12]
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Hazan, R. B., QIAO, R., Keren, R., Badano, I., & Suyama, K. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1294.016 · Cited by 595
Malignant melanoma: genetics and therapeutics in the genomic eraPreprint
Chin, L., Garraway, L. A., & Fisher, D. E. (2006) · Genes & Development · doi:10.1101/gad.1437206 · Cited by 524
c-Met: Structure, functions and potential for therapeutic inhibition
Ma, P. C., Maulik, G., Christensen, J. G., & Salgia, R. (2003) · Cancer and Metastasis Reviews · doi:10.1023/a:1023768811842 · Cited by 506
Melanoma: from mutations to medicine
Tsao, H., Chin, L., Garraway, L. A., & Fisher, D. E. (2012) · Genes & Development · doi:10.1101/gad.191999.112 · Cited by 496
The melanocyte differentiation program predisposes to metastasis after neoplastic transformation
Gupta, P. B., Kuperwasser, C., Brunet, J.-P., Ramaswamy, S., Kuo, W.-L., Gray, J. W., Naber, S. P., & Weinberg, R. A. (2005) · Nature Genetics · doi:10.1038/ng1634 · Cited by 451
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
- Venue
- Oncogene
- Published
- 2001-12-06
- Volume
- 20
- Issue
- 56
- Pages
- 8125-8135
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- 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
- 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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