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Reduced phosphorylation of Stat3 at Ser-727 mediated by casein kinase 2 — Protein phosphatase 2A enhances Stat3 Tyr-705 induced tumorigenic potential of glioma cells

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Title Reduced phosphorylation of Stat3 at Ser-727 mediated by casein kinase 2 — Protein phosphatase 2A enhances Stat3 Tyr-705 induced tumorigenic potential of glioma cells
 
Creator Mandal, Tapashi
Bhowmik, Arijit
Chatterjee, Anirban
Chatterjee, Uttara
Chatterjee, Uttara
Ghosh, Mrinal Kanti
 
Subject Cancer Biology and Inflammatory Disorder Division
 
Description Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is involved in cell survival
and proliferation and has been found to be persistently activated inmost human cancers mainly through its phosphorylation at Tyr-705. However, the role and regulation of Stat3 Ser-727 phosphorylation in cancer cells
have not been clearly evaluated. In our findings, correlation studies on the expression of CK2 and Stat3
Ser-727 phosphorylation levels in human glioma patient samples as well as rat orthotopic tumor model show
a degree of negative correlation. Moreover, brain tumor cell lines were treated with various pharmacological
inhibitors to inactivate the CK2 pathway. Here, increased Stat3 Ser-727 phosphorylation upon CK2 inhibition
was observed. Overexpression of CK2 (α, α′ or β subunits) by transient transfection resulted in decreased
Stat3 Ser-727 phosphorylation. Stat3 Tyr-705 residuewas conversely phosphorylated in similar situations. Interestingly, wefound PP2A, a protein phosphatase, to be amediator in the negative regulation of Stat3 Ser-727 phosphorylation by CK2. In vitro assays prove that Ser-727 phosphorylation of Stat3 affects the transcriptional activity of its downstream targets like SOCS3, bcl-xl and Cyclin D1. Stable cell lines constitutively expressing Stat3 S727A mutant showed increased survival, proliferation and invasionwhich are characteristics of a cancer cell. Rat tumor models generated with the Stat3 S727A mutant cell line formed more aggressive tumors when compared to the
Stat3WT expressing stable cell line. Thus, in glioma, reduced Stat3 Ser-727 phosphorylation enhances tumorigenicity which may be regulated in part by CK2–PP2A pathway
 
Publisher Elsevier
 
Date 2014
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2141/1/CELLULAR_SIGNALLING__V_26__(_8_)_1725%2D17342014[80].pdf
Mandal, Tapashi and Bhowmik, Arijit and Chatterjee, Anirban and Chatterjee, Uttara and Chatterjee, Uttara and Ghosh, Mrinal Kanti (2014) Reduced phosphorylation of Stat3 at Ser-727 mediated by casein kinase 2 — Protein phosphatase 2A enhances Stat3 Tyr-705 induced tumorigenic potential of glioma cells. Cellular Signalling, 26 (8). pp. 1725-1734.
 
Relation http://dx.doi.org/10.1016/j.cellsig.2014.04.003
http://www.eprints.iicb.res.in/2141/