Oncotarget

Research Papers:

Impact of STAT3 phosphorylation in glioblastoma stem cells radiosensitization and patient outcome

Konstantin Masliantsev, Baptiste Pinel, Anaïs Balbous, Pierre-Olivier Guichet, Gaëlle Tachon, Serge Milin, Julie Godet, Mathilde Duchesne, Antoine Berger, Christos Petropoulos, Michel Wager and Lucie Karayan-Tapon _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:3968-3979. https://doi.org/10.18632/oncotarget.23374

Metrics: PDF 561 views  |   HTML 872 views  |   ?  


Abstract

Konstantin Masliantsev1,2,3, Baptiste Pinel4, Anaïs Balbous1,2,3, Pierre-Olivier Guichet1,2,3, Gaëlle Tachon1,2,3, Serge Milin5, Julie Godet5, Mathilde Duchesne5, Antoine Berger4, Christos Petropoulos1,2,3, Michel Wager2,6 and Lucie Karayan-Tapon1,2,3

1Inserm U1084, Laboratoire de Neurosciences Expérimentales et Cliniques, Poitiers F-86073, France

2Université de Poitiers, Poitiers F-86073, France

3CHU de Poitiers, Laboratoire de Cancérologie Biologique, Poitiers F-86022, France

4CHU de Poitiers, Service d’Oncologie Radiothérapique, Poitiers F-86021, France

5CHU de Poitiers, Service d’Anatomo-Cytopathologie, Poitiers F-86021, France

6CHU de Poitiers, Service de Neurochirurgie, Poitiers F-86021, France

Correspondence to:

Lucie Karayan-Tapon, email: lucie.karayan-tapon@chu-poitiers.fr

Keywords: glioblastoma; Stat3; radioresistance; cancer stem cells; static

Received: October 26, 2017     Accepted: November 29, 2017     Published: December 16, 2017

ABSTRACT

Glioblastoma (GBM) represents the most common and lethal primary malignant brain tumor. The standard treatment for glioblastoma patients involves surgical resection with concomitant radio and chemotherapy. Despite today’s clinical protocol, the prognosis for patients remains very poor with a median survival of 15 months. Tumor resistance and recurrence is strongly correlated with a subpopulation of highly radioresistant and invasive cells termed Glioblastoma Stem Cells (GSCs). The transcription factor STAT3 has been found to be constitutively activated in different tumors including GBM and enhanced tumor radioresistance. In this study, we assessed radiosensitization of GSC lines isolated from patients by inhibition of STAT3 activation using Stattic or WP1066. We showed that inhibitor treatment before cell irradiation decreased the surviving fraction of GSCs suggesting that STAT3 inhibition could potentiate radiation effects. Finally, we investigated STAT3 activation status on 61 GBM clinical samples and found a preferential phosphorylation of STAT3 on Serine727 (pS727). Moreover, we found that pS727 was associated with a significant lower overall patient survival and progression-free survival but not pY705. Taken together, our results suggest that pS727-STAT3 could be a potential prognostic marker and could constitute a therapeutic target to sensitize highly radioresistant GSCs.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 23374