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PKC delta activated by c-MET enhances infiltration of human glioblastoma cells through NOTCH2 signaling

Title
PKC delta activated by c-MET enhances infiltration of human glioblastoma cells through NOTCH2 signaling
Author
이수재
Keywords
PKCd; infiltration; glioblastoma; NOTCH2; c-MET
Issue Date
2016-01
Publisher
IMPACT JOURNALS LLC
Citation
ONCOTARGET, v. 7, NO 4, Page. 4890-4902
Abstract
Poor prognosis of glioblastoma (GBM) is attributable to the propensity of tumor cells to infiltrate into the brain parenchyma. Protein kinase C (PKC) isozymes are highly expressed or aberrantly activated in GBM. However, how this signaling node translates to GBM cell invasiveness remains unknown. Here, we report that among PKC isoforms, PKC delta is strongly associated with infiltration of GBM cells. Notably, PKC delta enhanced Tyr418 phosphorylation of the non-receptor tyrosine kinase SRC, which in turn activated STAT3 and subsequent NOTCH2 signaling, ultimately leading to GBM cell invasiveness. Furthermore, we showed that PKC delta was aberrantly activated in GBM cells by c-MET, a receptor tyrosine kinase hyperactivated in GBM. In agreement, inhibition either component in the c-MET/PKC delta/SRC/STAT3 signaling axis effectively blocked the NOTCH2 signaling and invasiveness of GBM cells. Taken together, our findings shed a light on the signaling mechanisms behind the constitutive activation of PKC delta signaling in GBM.
URI
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=6640&path[]=18929http://hdl.handle.net/20.500.11754/30400
ISSN
1949-2553
DOI
10.18632/oncotarget.6640
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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