Inhibition of neurotrophin receptor p75 intramembran proteolysis by gamma-secretase inhibitor reduces medulloblastoma spinal metastasis

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• 作者：XiaoJi Wang ; Min Cui ; Lei Wang ; XueHong Chen ; Pan Xin
• 关键词：p75^NTR proteolysis ; Medulloblastoma spinal metastasis ; γ ; -Secretase inhibitor
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2010
• 出版时间：17 December 2010
• 年：2010
• 卷：403
• 期：3-4
• 页码：264-269
• 全文大小：480 K

文摘

Medulloblastoma (MB) is the most devastating and common pediatric brain tumor. Tumor cells invading into surrounding tissue and disseminating through cerebrospinal fluid make treatment extremely difficult. Identifying the mechanisms of MB cells is therefore imperative for the development of novel treatments. A research group demonstrated recently that the multifunctional signaling protein neurotrophin receptor p75^NTR is a central regulator for glioma invasion. γ-secretase mediated processing of the p75^NTR is a major contributor to the highly invasive nature of malignant gliomas. In this study we examine the p75^NTR expression and processing in medulloblastoma cells. Results show that p75^NTR is a critical regulator of medulloblastoma spinal metastasis. γ-secretase inhibitor, which blocks p75^NTR proteolytic processing, significantly abrogates p75^NTR induced medulloblastoma migration and invasion in vitro and in vivo. This data suggests that p75^NTR is also an important therapeutic target for MB. γ-secretase inhibitor may be a potentially effective clinical application for the treatment of medulloblastoma spinal metastasis.