Glioma derived isocitrate dehydrogenase-2 mutations induced up-regulation of HIF-1伪 and 尾-catenin signaling: Possible impact on glioma cell metastasis and chemo-resistance

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• 作者：Yuejun Fu^a ; ¹ ; ^{yjfu@sxu.edu.cn} ; Shuhua Zheng^a ; ¹ ; ^{zhengshuhua2009@live.cn} ; Yali Zheng^a ; ^{happyzhengyali@163.com} ; Rui Huang^a ; ^{200923002005@mail.sxu.cn} ; Na An^a ; ^{5632285@163.com} ; Aihua Liang^a ; ^{aliang@sxu.edu.cn} ; Changchen Hu^b ; ^c ; ^{hucc88@yahoo.com.cn}
• 关键词：Glioma ; Isocitrate dehydrogenase ; HIF-1伪 ; 尾-Catenin ; N-cadherin
• 刊名：The International Journal of Biochemistry and Cell Biology
• 出版年：2012
• 期刊代码：127_13572725
• 类别：med
• 出版时间：May, 2012
• 卷：44
• 期：5
• 页码：770-775
• 文件大小：961 K

摘要

The identification of heterozygous mutations (with an incidence up to 85%) in either the R132 residue of isocitrate dehydrogenase-1 (IDH1) or the R172 residue of IDH2 in human low-grade diffuse gliomas was remarkable because no oncogenic pathway had been previously documented correlated with these enzymes. In spite of a recent surge in elucidating the tumorigenic activity of IDH mutations in glioblastoma, the underlying biological mechanisms remain poorly understood. We showed here that C6 glioma cells transiently over-expressing IDH2^R172G induced nuclear accumulation of 尾-catenin, up-regulation of HIF-1伪 signaling and corresponding proteins expression that were closely related with tumor invasion and chemo-resistance. These results demonstrated a functional model in which IDH mutations were closely interrelated with glioma progression and could hold some therapeutic implications for future human glioma treatment.