CSTP1 inhibits IL-6 expression through targeting Akt/FoxO3a signaling pathway in bladder cancer cells.

CSTP1, a recently identified protein phosphotase, is frequently repressed in bladder cancers. Previous results showed that CSTP1 over-expression inhibited cell cycle progression and promoted apoptosis through dephosphorylating Akt kinase at Ser473 site in bladder cancer cells, but the mechanisms how CSTP1 exerted tumor suppressive activity remains unclear. In this study, we analyzed the gene expression profile changes that affected by CSTP1 overexpression by microarray, and reported that CSTP1 decreased IL-6 expression/secretion in bladder cancer cells and re-expression of IL-6 abrogated CSTP1's tumor suppressive activity. We also found that FoxO3a occupy IL-6 gene promoter and repressed IL mRNA transcription. Further results showed that decreased expression of IL-6 in CSTP1-overexpressing cells inactivated Stat3 transcriptional factor, which resulted in the down-regulation of cyclin D1, Bcl-xl expression. Spearman correlation analysis revealed that the mRNA level of CSTP1 correlated inversely with that of IL-6 in bladder cancer tissues. In conclusion, our studies revealed that protein phosphotase CSTP1 inhibited IL-6 expression through targeting Akt/FoxO3a signaling pathway and IL-6 inactivated Stat3 was necessary for CSTP1's tumor suppressive function.