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 β 1 mediated invasion of glioma cells.
Methods: In order to investigate whether the down-regulation of Hsc70 would affect the expression of integrin β 1 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 β 1 in human glioma cells. Cellular localization of integrin β 1 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 β 1 without changing its mRNA. Meanwhile, the integrin β 1 125-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 β 1, strengthened its interaction with integrin α 5 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 β 1 and subsequently inhibit glioma invasion phenotype.
Keywords: Hsc70, integrin β 1, glioma, focal adhesion kinase, invasion