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Cited by 33Glioma Diagnosis and TreatmentCytokine Signaling Pathways and InteractionsCancer, Hypoxia, and Metabolism

STAT3 Serine 727 Phosphorylation: A Relevant Target to Radiosensitize Human Glioblastoma

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Ouédraogo, Zangbéwendé Guy, Müller‐Barthélémy, Mélanie, Kemeny, Jean‐Louis, Dedieu, Véronique, Biau, Julian, Khalil, Toufic, Raoelfils, Lala Ines, Granzotto, Adeline +7 more·2016·Brain Pathology
DOI 10.1111/bpa.12254PMC PMC8029431
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Abstract

Radiotherapy is an essential component of glioma standard treatment. Glioblastomas (GBM), however, display an important radioresistance leading to tumor recurrence. To improve patient prognosis, there is a need to radiosensitize GBM cells and to circumvent the mechanisms of resistance caused by interactions between tumor cells and their microenvironment. STAT3 has been identified as a therapeutic target in glioma because of its involvement in mechanisms sustaining tumor escape to both standard treatment and immune control. Here, we studied the role of STAT3 activation on tyrosine 705 (Y705) and serine 727 (S727) in glioma radioresistance. This study explored STAT3 phosphorylation on Y705 (pSTAT3‐Y705) and S727 (pSTAT3‐S727) in glioma cell lines and in clinical samples. Radiosensitizing effect of STAT3 activation down‐modulation by Gö6976 was explored. In a panel of 15 human glioma cell lines, we found that the level of pSTAT3‐S727 was correlated to intrinsic radioresistance. Moreover, treating GBM cells with Gö6976 resulted in a highly significant radiosensitization associated to a concomitant pSTAT3‐S727 down‐modulation only in GBM cell lines that exhibited no or weak pSTAT3‐Y705. We report the constitutive activation of STAT3‐S727 in all GBM clinical samples. Targeting pSTAT3‐S727 mainly in pSTAT3‐Y705‐negative GBM could be a relevant approach to improve radiation therapy.

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Authors
Ouédraogo, Z. G., Müller‐Barthélémy, M., Kemeny, J., Dedieu, V., Biau, J., Khalil, T., Raoelfils, L. I., Granzotto, A., Pereira, B., Beaudoin, C., Guissou, I. P., Berger, M., Morel, L., Chautard, E., & Verrelle, P.
Affiliations
  • Clermont Université, Université d′Auvergne EA 7283, CREaT, BP 10448 F‐63000 CLERMONT‐FERRAND France
  • Centre National de la Recherche Scientifique (FR)
  • Université Clermont Auvergne (FR)
  • Centre Jean Perrin Service D'anatomopathologie F‐63000 CLERMONT‐FERRAND France
  • Inserm (FR)
  • Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
  • Université Joseph Ki-Zerbo (BF)
ORCID
Venue
Brain Pathology
Publisher
Wiley
Published
2015-04-30
Volume
26
Issue
1
Pages
18-30
ISSN
  • 1015-6305 (ISSN-L)
  • 1750-3639
DOI
10.1111/bpa.12254
PMC
PMC8029431
OpenAlex
W2096472936
Cited by
33
References
5
Citations by year
2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 6 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 1
FWCI
2.61
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Brain Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Ligue Nationale Contre le Cancer (Comité du Puy-De-Dôme)
  • Institut National du Cancer
  • Region Auvergne
  • Ministère des Enseignements Secondaire et Supérieur, Burkina Faso
Topics
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
STAT3, serine 727 phosphorylation, tyrosine 705 phosphorylation, glioblastoma, radiosensitization, radioresistance (biology), Gö6976, STAT3 inhibitor, tumor microenvironment, radiotherapy
MeSH terms
Brain Neoplasms, Carbazoles, Colony-Forming Units Assay, Dose-Response Relationship, Drug, Enzyme Inhibitors, Glioblastoma, Humans, Phosphorylation, Radiation, Radiation Tolerance, Serine, Spectrophotometry, Time Factors, X-Rays, Signal Transduction, Gene Expression Regulation, Neoplastic, Statistics, Nonparametric, Cell Line, Tumor, Cell Proliferation, STAT3 Transcription Factor

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