GSK3 and PKB/Akt are associated with integrin‐mediated regulation of PTHrP, IL‐6 and IL‐8 expression in FG pancreatic cancer cells

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Abstract
We have demonstrated recently that PTHrP is upregulated in pancreatic adenocarcinoma and that the ECM exerts regulatory control, at least in part, over PTHrP expression. In our present study, we examined the potential signaling interactions between these 2 pathways. Our results demonstrate that, under serum‐free conditions, adhesion of FG pancreatic adenocarcinoma cells on Fn is mediated by the α5β1 integrin, whereas adhesion to Type I collagen is mediated by the α2β1 integrin. α5β1 integrin‐mediated adhesion to Fn results in a phenotype that includes a reduction in cell proliferation, increased E‐cadherin localization in cell–cell contacts, increased β‐catenin localization throughout the cell, inhibition of haptokinetic cell migration, and increased expression of PTHrP, IL‐6 and IL‐8 relative to α2β1 integrin‐mediated adhesion on Type I collagen. A phosphoprotein immunoblotting screen of FG pancreatic cancer cells grown on either Fn or Type I collagen indicates that GSK3 and PKB/Akt are differentially phosphorylated on these 2 substrates. These results implicate GSK3 and PKB/Akt in the integrin‐mediated regulation of PTHrP, IL‐6 and IL‐8 in pancreatic cancer.

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