N-cadherin/FGFR promotes metastasis through epithelial-to-mesenchymal transition and stem/progenitor cell-like properties Journal Article
| Authors: | Qian, X.; Anzovino, A.; Kim, S.; Suyama, K.; Yao, J.; Hulit, J.; Agiostratidou, G.; Chandiramani, N.; McDaid, H. M.; Nagi, C.; Cohen, H. W.; Phillips, G. R.; Norton, L.; Hazan, R. B. |
| Article Title: | N-cadherin/FGFR promotes metastasis through epithelial-to-mesenchymal transition and stem/progenitor cell-like properties |
| Abstract: | N-cadherin and HER2/neu were found to be co-expressed in invasive breast carcinomas. To test the contribution of N-cadherin and HER2 in mammary tumor metastasis, we targeted N-cadherin expression in the mammary epithelium of the MMTV-Neu mouse. In the context of ErbB2/Neu, N-cadherin stimulated carcinoma cell invasion, proliferation and metastasis. N-cadherin caused fibroblast growth factor receptor (FGFR) upmodulation, resulting in epithelial-to-mesenchymal transition (EMT) and stem/progenitor like properties, involving Snail and Slug upregulation, mammosphere formation and aldehyde dehydrogenase activity. N-cadherin potentiation of the FGFR stimulated extracellular signal regulated kinase (ERK) and protein kinase B (AKT) phosphorylation resulting in differential effects on metastasis. Although ERK inhibition suppressed cyclin D1 expression, cell proliferation and stem/progenitor cell properties, it did not affect invasion or EMT. Conversely, AKT inhibition suppressed invasion through Akt 2 attenuation, and EMT through Snail inhibition, but had no effect on cyclin D1 expression, cell proliferation or mammosphere formation. These findings suggest N-cadherin/FGFR has a pivotal role in promoting metastasis through differential regulation of ERK and AKT, and underscore the potential for targeting the FGFR in advanced ErbB2-amplified breast tumors. © 2014 Macmillan Publishers Limited All rights reserved. |
| Keywords: | mitogen activated protein kinase; protein kinase b; controlled study; protein expression; human cell; nonhuman; cell proliferation; animal cell; mouse; mesenchyme cell; metastasis; enzyme inhibition; protein targeting; animal experiment; animal model; stem cell; cell transformation; nerve cell adhesion molecule; breast epithelium; upregulation; cyclin d1; transcription factor slug; erbb2; transcription factor snail; cell invasion; mouse mammary tumor virus; fibroblast growth factor receptor 1; aldehyde dehydrogenase; gastropoda; n-cadherin; human; priority journal; article; fgfr; mammospheres |
| Journal Title: | Oncogene |
| Volume: | 33 |
| Issue: | 26 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2014-06-26 |
| Start Page: | 3411 |
| End Page: | 3421 |
| Language: | English |
| DOI: | 10.1038/onc.2013.310 |
| PROVIDER: | scopus |
| PMCID: | PMC4051865 |
| PUBMED: | 23975425 |
| DOI/URL: | |
| Notes: | Cited By (since 1996):2 -- Export Date: 1 August 2014 -- CODEN: ONCNE -- Source: Scopus |
