Lyn modulates Claudin-2 expression and is a therapeutic target for breast cancer liver metastasis.
Oncotarget
; 6(11): 9476-87, 2015 Apr 20.
Article
em En
| MEDLINE
| ID: mdl-25823815
ABSTRACT
Claudin-2 enhances breast cancer liver metastasis and promotes the development of colorectal cancers. The objective of our current study is to define the regulatory mechanisms controlling Claudin-2 expression in breast cancer cells. We evaluated the effect of several Src Family Kinase (SFK) inhibitors or knockdown of individual SFK members on Claudin-2 expression in breast cancer cells. We also assessed the potential effects of pan-SFK and SFK-selective inhibitors on the formation of breast cancer liver metastases. This study reveals that pan inhibition of SFK signaling pathways significantly elevated Claudin-2 expression levels in breast cancer cells. In addition, our data demonstrate that pan-SFK inhibitors can enhance breast cancer metastasis to the liver. Knockdown of individual SFK members reveals that loss of Yes or Fyn induces Claudin-2 expression; whereas, diminished Lyn levels impairs Claudin-2 expression in breast cancer cells. The Lyn-selective kinase inhibitor, Bafetinib (INNO-406), acts to reduce Claudin-2 expression and suppress breast cancer liver metastasis. Our findings may have major clinical implications and advise against the treatment of breast cancer patients with broad-acting SFK inhibitors and support the use of Lyn-specific inhibitors.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carcinoma
/
Regulação Neoplásica da Expressão Gênica
/
Quinases da Família src
/
Claudinas
/
Terapia de Alvo Molecular
/
Neoplasias de Mama Triplo Negativas
/
Neoplasias Hepáticas
/
Neoplasias Mamárias Experimentais
/
Proteínas de Neoplasias
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article