Cobalt chloride에 의해 유도되는 상피-중간엽 이행에서의 국소부착 단백질의 인산화의 역할 규명

Abstract

Hypoxia is a common condition found in a wide range of solid tumors and is often associated with metastasis and poor clinical outcomes. In the present study, we found that HIF- was induced by cobalt chloride (500 ) treatment on human lung cancer cells, A549 and H460, for 24 hr. However, cobalt chloride (500 ) did not affect cell proliferation of A549 and H460 in 48 hr. Cobalt chloride (500 ) additionally induced epithelial-to-mesenchymal-like transition (EMT) such as reduced E-cadherin expression and increased -SMA expression. These results were confirmed by immunofluorecence experiment in H460 cells. E-cadherin was localized on the outer cell membrane. However, when the cells were treated with 500 cobalt chloride for 24 hr, diffuse E-cadherin staining was observed, characteristic of a migratory mesenchymal phenotype. We also found that cobalt chloride induced integrin expression and FAK phosphorylation in human lung cancer cells using western blotting and FACS anlaysis. Our data suggest that integrin -induced FAK phosphorylation may be developed into target molecules for blocking tumor metastasis.