LIM-homeobox gene 2 promotes tumor growth and metastasis by inducing autocrine and paracrine PDGF-B signaling.
Mol Oncol
; 8(2): 401-16, 2014 Mar.
Article
en En
| MEDLINE
| ID: mdl-24423492
ABSTRACT
An epithelial-mesenchymal transition (EMT) is a critical process during embryonic development and the progression of epithelial tumors to metastatic cancers. Gene expression profiling has uncovered the transcription factor LIM homeobox gene 2 (Lhx2) with up-regulated expression during TGFß-induced EMT in normal and cancerous breast epithelial cells. Loss and gain of function experiments in transgenic mouse models of breast cancer and of insulinoma in vivo and in breast cancer cells in vitro indicate that Lhx2 plays a critical role in primary tumor growth and metastasis. Notably, the transgenic expression of Lhx2 during breast carcinogenesis promotes vessel maturation, primary tumor growth, tumor cell intravasation and metastasis by directly inducing the expression of platelet-derived growth factor (PDGF)-B in tumor cells and by indirectly increasing the expression of PDGF receptor-ß (PDGFRß) on tumor cells and pericytes. Pharmacological inhibition of PDGF-B/PDGFRß signaling reduces vessel functionality and tumor growth and Lhx2-induced cell migration and cell invasion. The data indicate a dual role of Lhx2 during EMT and tumor progression by inducing the expression of PDGF-B, Lhx2 provokes an autocrine PDGF-B/PDGFRß loop required for cell migration, invasion and metastatic dissemination and paracrine PDGF-B/PDGFRß signaling to support blood vessel functionality and, thus, primary tumor growth.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Neoplasias de la Mama
/
Transducción de Señal
/
Comunicación Autocrina
/
Comunicación Paracrina
/
Proteínas Proto-Oncogénicas c-sis
/
Proteínas con Homeodominio LIM
/
Neoplasias Mamarias Experimentales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Mol Oncol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2014
Tipo del documento:
Article
País de afiliación:
Suiza