Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Akt/protein kinase B is a pivotal component downstream of phosphatidylinositol 3-kinase (PI3K) pathway, whose activity regulates the balance between cell survival and apoptosis. Phosphorylation of Akt occurs at two key sites either at Thr308 site in the activation loop or at Ser473 site in the hydrophobic motif. The phosphorylated form of Akt (pAkt) is activated to promote cell survival. The mechanisms of pAkt dephosphorylation and how the signal transduction of Akt pathway is terminated are still largely unknown. In this study, we identified a novel protein phosphatase CSTP1(complete s transactivated protein 1), which interacts and dephosphorylates Akt specifically at Ser473 site in vivo and in vitro, blocks cell cycle progression and promotes cell apoptosis. The effects of CSTP1 on cell survival and cell cycle were abrogated by depletion of phosphatase domain of CSTP1 or by expression of a constitutively active form of Akt (S473D), suggesting Ser473 site of Akt as a primary cellular target of CSTP1. Expression profile analysis showed that CSTP1 expression is selectively down-regulated in non-invasive bladder cancer tissues and over-expression of CSTP1 suppressed the size of tumors in nude mice. Kaplan-Meier curves revealed that decreased expression of CSTP1 implicated significantly reduced recurrence-free survival in patients suffered from non-invasive bladder cancers.
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PMID:CSTP1, a novel protein phosphatase, blocks cell cycle, promotes cell apoptosis, and suppresses tumor growth of bladder cancer by directly dephosphorylating Akt at Ser473 site. 2379 35

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.
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PMID:CSTP1 inhibits IL-6 expression through targeting Akt/FoxO3a signaling pathway in bladder cancer cells. 3100 15