An in vivo model of epithelial to mesenchymal transition reveals a mitogenic switch.
Cancer Lett
; 326(2): 183-90, 2012 Dec 30.
Article
en En
| MEDLINE
| ID: mdl-22906417
ABSTRACT
The epithelial to mesenchymal transition (EMT) is a process by which differentiated epithelial cells transition to a mesenchymal phenotype. EMT enables the escape of epithelial cells from the rigid structural constraints of the tissue architecture to a phenotype more amenable to cell migration and, therefore, invasion and metastasis. We characterized an in vivo model of EMT and discovered that marked changes in mitogenic signaling occurred during this process. DNA microarray analysis revealed that the expression of a number of genes varied significantly between post-EMT and pre-EMT breast cancer cells. Post-EMT cancer cells upregulated mRNA encoding c-Met and the PDGF and LPA receptors, and acquired increased responsiveness to HGF, PDGF, and LPA. This rendered the post-EMT cells responsive to the growth inhibitory effects of HGF, PDGF, and LPA receptor inhibitors/antagonists. Furthermore, post-EMT cells exhibited decreased basal Raf and Erk phosphorylation, and in comparison to pre-EMT cells, their proliferation was poorly inhibited by a MEK inhibitor. These studies suggest that therapies need to be designed to target both pre-EMT and post-EMT cancer cells and that signaling changes in post-EMT cells may allow them to take advantage of paracrine signaling from the stroma in vivo.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Transición Epitelial-Mesenquimal
/
Mitógenos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos