Hepatocyte growth factor differently influences Met-E-cadherin phosphorylation and downstream signaling pathway in two models of breast cells

E-cadherins are implicated in cell adhesion, and also in cell signaling by associating with tyrosine kinase-receptors such as Met, the hepatocyte growth factor (HGF) receptor. Using two different cellular models, i.e. MCF-7 (breast carcinoma) and MCF-10 (immortalized mammary) cells, we studied the p...

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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2006-09, Vol.63 (17), p.2016-2026
Main Authors: Matteucci, E, Ridolfi, E, Desiderio, M A
Format: Article
Language:English
Subjects:
beta Catenin - genetics
beta Catenin - metabolism
Breast cancer
Breast Neoplasms - metabolism
Cadherins - metabolism
Cell adhesion & migration
Cell Line, Transformed
Cell Line, Tumor
Female
Hepatocyte Growth Factor - pharmacology
Humans
Kinases
Models, Biological
Molecular biology
Phosphatidylinositol 3-Kinases - genetics
Phosphatidylinositol 3-Kinases - physiology
Phosphorylation
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-met
Proto-Oncogene Proteins pp60(c-src) - genetics
Proto-Oncogene Proteins pp60(c-src) - physiology
Receptors, Growth Factor - metabolism
Signal Transduction
TCF Transcription Factors - metabolism
Transcriptional Activation
Transfection
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Summary:E-cadherins are implicated in cell adhesion, and also in cell signaling by associating with tyrosine kinase-receptors such as Met, the hepatocyte growth factor (HGF) receptor. Using two different cellular models, i.e. MCF-7 (breast carcinoma) and MCF-10 (immortalized mammary) cells, we studied the possible mechanism(s) by which E-cadherins modulate the signaling pathways downstream of Met, leading to beta-catenin-TCF transcriptional activity. In MCF-7, but not in MCF-10 cells, E-cadherins were remarkably associated with Met. Moreover, in MCF-7 cells both co-immunoprecipitation with anti-Met antibody and co-localization were increased by 30-min HGF treatment, which caused E-cadherin tyrosine phosphorylation. Also beta-catenin in the co-immunoprecipitate was phosphorylated by HGF, probably favoring TCF activation. Consistently, after HGF treatment, beta-catenin redistributed earlier in MCF-7 than in MCF-10 cells, with nuclear accumulation and activation of TOPFLASH gene reporter. Our results indicate a functional role of Met-E-cadherin interaction in MCF-7 cells through the amplification of the signaling downstream of HGF-Met triggering that involved c-Src and phosphoinositide-3-kinase activities.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-006-6137-0