Impact of STAT3 phosphorylation in glioblastoma stem cells radiosensitization and patient outcome
| Autor: | Serge Milin, Julie Godet, Baptiste Pinel, Konstantin Masliantsev, Gaëlle Tachon, Pierre-Olivier Guichet, Michel Wager, Mathilde Duchesne, Antoine Berger, Christos Petropoulos, Lucie Karayan-Tapon, Anais Balbous |
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| Přispěvatelé: | Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Oncologie Hématologique et de Thérapie Cellulaire [Poitiers], Laboratoire Cancérologie Biologique Poitiers, Cibles moléculaires et thérapeutiques de la maladie d'Alzheimer (CIMoTHeMA), Université de Poitiers, Département d'Anatomocytopathologie, Service d’Oncologie Hématologique et Thérapie Cellulaire [CHU Poitiers], Cellules souches leucémiques et thérapeuthiques, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers) |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
cancer stem cells medicine.medical_treatment Cell [SDV.CAN]Life Sciences [q-bio]/Cancer 03 medical and health sciences 0302 clinical medicine static Cancer stem cell Radioresistance Medicine STAT3 Chemotherapy biology Stat3 business.industry glioblastoma 3. Good health radioresistance 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Concomitant Cancer research biology.protein Phosphorylation Stem cell business Research Paper |
| Zdroj: | Oncotarget Oncotarget, Impact journals, 2018, 9 (3), pp.3968-3979. ⟨10.18632/oncotarget.23374⟩ |
| ISSN: | 1949-2553 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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