GPCR-induced migration of breast carcinoma cells depends on both EGFR signal transactivation and EGFR-independent pathways.
Biol Chem
; 386(9): 845-55, 2005 Sep.
Article
em En
| MEDLINE
| ID: mdl-16164409
ABSTRACT
The epidermal growth factor receptor (EGFR) plays a key role in the regulation of important cellular processes under normal and pathophysiological conditions such as cancer. In human mammary carcinomas the EGFR is involved in regulating cell growth, survival, migration and metastasis and its activation correlates with the lack of response in hormone therapy. Here, we demonstrate in oestrogen receptor-positive and -negative human breast cancer cells and primary mammary epithelial cells a cross-communication between G protein-coupled receptors (GPCRs) and the EGFR. We present evidence that specific inhibition of ADAM15 or TACE blocks GPCR-induced and proHB-EGF-mediated EGFR tyrosine phosphorylation, downstream mitogenic signalling and cell migration. Notably, activation of the PI3K downstream mediator PKB/Akt by GPCR ligands involves the activity of sphingosine kinase (SPHK) and is independent of EGFR signal transactivation. We conclude that GPCR-induced chemotaxis of breast cancer cells is mediated by EGFR-dependent and -independent signalling pathways, with both parallel pathways having to act in concert to achieve a complete migratory response.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Movimento Celular
/
Receptores Acoplados a Proteínas G
/
Receptores ErbB
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article