Open AccessTargeting EYA2 tyrosine phosphatase activity in glioblastoma stem cells induces mitotic catastrophe
Author(s) -
Guoxin Zhang,
Zhen Dong,
Ryan C. Gimple,
Arthur Wolin,
Qiulian Wu,
Zhixin Qiu,
Lisa M Wood,
Jia Shen,
Li Jiang,
Linjie Zhao,
Deguan Lv,
Briana C. Prager,
Leo J.Y. Kim,
Xiuxing Wang,
Lingdi Zhang,
Ryan L. Anderson,
Jeffrey K. Moore,
Shideng Bao,
Thomas H. Keller,
Grace Lin,
CongBao Kang,
Petra Hamerlik,
Rui Zhao,
Heide L. Ford,
Jeremy Rich
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20202669
Subject(s) - neural stem cell , stem cell , biology , cancer research , mitosis , mitotic catastrophe , microbiology and biotechnology , cell cycle , apoptosis , genetics
Glioblastoma ranks among the most lethal of primary brain malignancies, with glioblastoma stem cells (GSCs) at the apex of tumor cellular hierarchies. Here, to discover novel therapeutic GSC targets, we interrogated gene expression profiles from GSCs, differentiated glioblastoma cells (DGCs), and neural stem cells (NSCs), revealing EYA2 as preferentially expressed by GSCs. Targeting EYA2 impaired GSC maintenance and induced cell cycle arrest, apoptosis, and loss of self-renewal. EYA2 displayed novel localization to centrosomes in GSCs, and EYA2 tyrosine (Tyr) phosphatase activity was essential for proper mitotic spindle assembly and survival of GSCs. Inhibition of the EYA2 Tyr phosphatase activity, via genetic or pharmacological means, mimicked EYA2 loss in GSCs in vitro and extended the survival of tumor-bearing mice. Supporting the clinical relevance of these findings, EYA2 portends poor patient prognosis in glioblastoma. Collectively, our data indicate that EYA2 phosphatase function plays selective critical roles in the growth and survival of GSCs, potentially offering a high therapeutic index for EYA2 inhibitors.