Heat Shock Cognate Protein 70 Enhanced Integrin β1 Mediated Invasion in Cancer Cells.

PURPOSE

Glioblastoma is one of the most common malignant cancers worldwide. In our previous work, we have shown that heat shock cognate protein 70 (Hsc70) functions as a positive growth regulator in glioma. We investigated the role of Hsc70 in integrin β1 mediated invasion of glioma cells.

METHODS

In order to investigate whether the down-regulation of Hsc70 would affect the expression of integrin β1 subunit, HeLa cells were transiently transfected with Hsc70-AS or pcDNA3.0 vectors and the down-regulation of Hsc70 was confirmed by Western blotting. Human brain glioma U87 cells were stably transfected with Hsc70-AS or pcDNA3.0 vectors to further elucidate the relationship between Hsc70 and integrin β1 in human glioma cells. Cellular localization of integrin β1 was detected using immunofluorescence confocal microscopy analysis.

RESULTS

Here we reported that down-regulation of the expression of Hsc70 in U87 cells by transfection with antisense cDNA specifically increased the expression of cell surface integrin β1 without changing its mRNA. Meanwhile, the integrin β1 125-kD mature form increased while 105-kD precursor form decreased when Hsc70 was down-regulated. Mechanically, the U87 cells transfected with antisense cDNA of Hsc70 decreased the Golgi localization of integrin β1, strengthened its interaction with integrin α5 subunit, and enhanced the adhesion ability to fibronectin (FN) and the phosphorylation level of focal adhesion kinase (FAK).

CONCLUSION

Overall, these results suggested that the down-regulation of Hsc70 expression could promote the expression of cell surface integrin β1 and subsequently inhibit glioma invasion phenotype.