PTK6 activation at the membrane regulates epithelial-mesenchymal transition in prostate cancer.
Cancer Res
; 73(17): 5426-37, 2013 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-23856248
ABSTRACT
The intracellular tyrosine kinase protein tyrosine kinase 6 (PTK6) lacks a membrane-targeting SH4 domain and localizes to the nuclei of normal prostate epithelial cells. However, PTK6 translocates from the nucleus to the cytoplasm in human prostate tumor cells. Here, we show that while PTK6 is located primarily within the cytoplasm, the pool of active PTK6 in prostate cancer cells localizes to membranes. Ectopic expression of membrane-targeted active PTK6 promoted epithelial-mesenchymal transition in part by enhancing activation of AKT, thereby stimulating cancer cell migration and metastases in xenograft models of prostate cancer. Conversely, siRNA-mediated silencing of endogenous PTK6 promoted an epithelial phenotype and impaired tumor xenograft growth. In mice, PTEN deficiency caused endogenous active PTK6 to localize at membranes in association with decreased E-cadherin expression. Active PTK6 was detected at membranes in some high-grade human prostate tumors, and PTK6 and E-cadherin expression levels were inversely correlated in human prostate cancers. In addition, high levels of PTK6 expression predicted poor prognosis in patients with prostate cancer. Our findings reveal novel functions for PTK6 in the pathophysiology of prostate cancer, and they define this kinase as a candidate therapeutic target. Cancer Res; 73(17); 5426-37. ©2013 AACR.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Proteínas Tirosina Quinases
/
Membrana Celular
/
PTEN Fosfo-Hidrolase
/
Proteínas Proto-Oncogênicas c-akt
/
Transição Epitelial-Mesenquimal
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos