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

被引：26

作者：

Ouedraogo, Zangbewende Guy ^{[1
,2
,3
]}

Mueller-Barthelemy, Melanie ^{[1
,2
]}

Kemeny, Jean-Louis ^{[1
,4
]}

Dedieu, Veronique ^{[1
,2
]}

Biau, Julian ^{[1
,2
,5
]}

Khalil, Toufic ^{[6
,7
]}

Raoelfils, Lala Ines ^{[8
]}

Granzotto, Adeline ^{[9
]}

Pereira, Bruno ^{[10
]}

Beaudoin, Claude ^{[11
,12
]}

Guissou, Innocent Pierre ^{[3
]}

Berger, Marc ^{[1
,13
]}

Morel, Laurent ^{[11
,12
]}

Chautard, Emmanuel ^{[1
,2
]}

Verrelle, Pierre ^{[1
,2
]}

机构：

[1] Univ Auvergne, Clermont Univ, EA 7283, CREaT, BP 10448, F-63000 Clermont Ferrand, France

[2] Ctr Jean Perrin, Serv Radiotherapie, Lab Radiooncol Expt, F-63000 Clermont Ferrand, France

[3] Univ Ouagadougou, Lab Pharmacol Toxicol & Chim Therapeut, 03 BP 7021, Ouagadougou 03, Burkina Faso

[4] CHU Clermont Ferrand, Serv Anatomopathol, F-63003 Clermont Ferrand, France

[5] INSERM, CNRS,U2021, UMR3347, Inst Curie, F-91405 Orsay, France

[6] CHU Clermont Ferrand, Serv Neurochirurg, F-63003 Clermont Ferrand, France

[7] Univ Auvergne, Clermont Univ, EA 7282, IGCNC, BP 10448, F-63000 Clermont Ferrand, France

[8] Ctr Jean Perrin, Serv Anatomopathol, F-63000 Clermont Ferrand, France

[9] INSERM, UMR1052, Radiobiol Grp, Lyon, France

[10] CHU Clermont Ferrand, DRCI, Biostat Unit, F-63003 Clermont Ferrand, France

[11] Univ Blaise Pascal, Clermont Univ, GReD, UMR CNRS 6293,INSERM,U1103, 24 Ave Landais,BP80026, F-63177 Aubiere, France

[12] Univ Blaise Pascal, Clermont Univ, GReD, UMR CNRS 6293,INSERM,U1103, 24 Ave Landais,BP80026, F-63171 Aubiere, France

[13] CHU Clermont Ferrand, Serv Hematol Biol Immunol, F-63003 Clermont Ferrand, France

来源：

BRAIN PATHOLOGY | 2016年 / 26卷 / 01期

关键词：

glioma; Go6976; radiotherapy; resistance; STAT3; ACUTE-PHASE RESPONSE; SIGNAL TRANSDUCER; CELL-PROLIFERATION; POTENT INHIBITOR; GROWTH-FACTOR; DNA-DAMAGE; IN-VITRO; ACTIVATION; GLIOMA; EXPRESSION;

D O I：

10.1111/bpa.12254

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 Go6976 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 Go6976 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.

引用

页码：18 / 30

页数：13

共 66 条

[21] NOTCH Pathway Blockade Depletes CD133-Positive Glioblastoma Cells and Inhibits Growth of Tumor Neurospheres and Xenografts [J].