Emx2 as a novel tool to suppress glioblastoma

被引:15
|
作者
Falcone, Carmen [1 ]
Daga, Antonio [2 ]
Leanza, Giampiero [3 ]
Mallamaci, Antonello [1 ]
机构
[1] SISSA, Dept Neurosci, I-34136 Trieste, Italy
[2] IRCCS AOU San Martino IST, DIPOE, I-16132 Genoa, Italy
[3] Univ Trieste, Dept Life Sci, I-34127 Trieste, Italy
关键词
Emx2; glioblastoma; gene therapy; EGFR; SOX2; CEREBRAL-CORTEX; STEM-CELLS; MUTANT MICE; CANCER; HES1; PROLIFERATION; PRIMORDIUM; PRECURSORS; INHIBIT; NEURONS;
D O I
10.18632/oncotarget.9322
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Glioblastoma is a devastating CNS tumour for which no cure is presently available. We wondered if manipulation of Emx2, which normally antagonizes cortico-cerebral astrogenesis by inhibiting proliferation of astrocyte progenitors, may be employed to counteract it. We found that Emx2 overexpression induced the collapse of seven out of seven in vitro tested glioblastoma cell lines. Moreover, it suppressed four out of four of these lines in vivo. As proven by dedicated rescue assays, the antioncogenic activity of Emx2 originated from its impact on at least six metabolic nodes, which accounts for the robustness of its effect. Finally, in two out of two tested lines, the tumor culture collapse was also achieved when Emx2 was driven by a neural stem cell specific promoter, likely active within tumor-initiating cells. All that points to Emx2 as a novel, promising tool for therapy of glioblastoma and prevention of its recurrencies.
引用
收藏
页码:41005 / 41016
页数:12
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