uPAR and cathepsin B-mediated compartmentalization of JNK regulates the migration of glioma-initiating cells.

Abstract:

: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.

journal_name

Stem Cell Res

journal_title

Stem cell research

authors

Alapati K,Kesanakurti D,Rao JS,Dasari VR

doi

10.1016/j.scr.2014.02.008

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

716-29

issue

3

eissn

1873-5061

issn

1876-7753

pii

S1873-5061(14)00025-7

journal_volume

12

pub_type

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