کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2094533 1082026 2014 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
uPAR and cathepsin B-mediated compartmentalization of JNK regulates the migration of glioma-initiating cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
uPAR and cathepsin B-mediated compartmentalization of JNK regulates the migration of glioma-initiating cells
چکیده انگلیسی


• uPAR and cathepsin B activate JNK pathway in regulating glioma cell migration.
• Overexpression of uPAR and cathepsin B increases expression of cytosolic p-JNK.
• Depletion of cytosolic p-JNK inhibits migration of glioma cells.
• Glioma cells utilize cytosolic p-JNK in driving the cells towards migration.

In the present study, we investigated the effect of simultaneous downregulation of uPAR and cathepsin B (pUC), alone or in combination with radiation, on JNK–MAPK signaling pathway in regulating the migration of non-GICs (glioma-initiating cells) and GICs. The increase in the expression of p-JNK with pUC treatment was mostly localized to nucleus whereas increase in the expression of p-JNK with radiation and overexpression of uPAR and cathepsin B was confined to cytoplasm of the cells. Depletion of cytosolic p-JNK with pUC treatment inhibited migration by downregulating the expression of the adapter proteins of the focal adhesion complex. We also observed that knockdown of uPAR and cathepsin B regulated the Ras–Pak-1 pathway to induce the translocation of p-JNK from cytosol to nucleus. In control cells, Pak-1 served as a functional inhibitor for MEKK-1, which inhibits the complex formation of MEKK-1 and p-JNK and thus inhibits the translocation of this complex into nucleus. Hence, we conclude that glioma cells utilize the availability of cytosolic p-JNK in driving the cells towards migration. Finally, treating the cells with pUC alone or in combination with radiation induced the translocation of the MEKK-1-p-JNK complex from cytosol to nucleus, thereby inhibiting the migration of glioma cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Stem Cell Research - Volume 12, Issue 3, May 2014, Pages 716–729
نویسندگان
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