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

Eunji Hwang, Ki Chun Yoo, Seok Gu Kang, Rae Kwon Kim, Yan Hong Cui, Hae June Lee, Min Jung Kim, Jae Seong Lee, In Gyu Kim, Yongjoon Suh, Su Jae Lee

Research output: Contribution to journalArticle

6 Citations (Scopus)

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, PKCδ is strongly associated with infiltration of GBM cells. Notably, PKCδ 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 PKCδ 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/PKCδ/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 PKCδ signaling in GBM.

Original languageEnglish
Pages (from-to)4890-4902
Number of pages13
JournalOncotarget
Volume7
Issue number4
DOIs
Publication statusPublished - 2016 Jan 1

Fingerprint

Glioblastoma
Protein Kinase C
Proto-Oncogene Proteins c-met
Protein-Tyrosine Kinases
Isoenzymes
Protein Isoforms
Phosphorylation
Brain

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Hwang, Eunji ; Yoo, Ki Chun ; Kang, Seok Gu ; Kim, Rae Kwon ; Cui, Yan Hong ; Lee, Hae June ; Kim, Min Jung ; Lee, Jae Seong ; Kim, In Gyu ; Suh, Yongjoon ; Lee, Su Jae. / PKCδ activated by c-MET enhances infiltration of human glioblastoma cells through NOTCH2 signaling. In: Oncotarget. 2016 ; Vol. 7, No. 4. pp. 4890-4902.
@article{43f38a4f1b6645079c990e4ce50482b0,
title = "PKCδ activated by c-MET enhances infiltration of human glioblastoma cells through NOTCH2 signaling",
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, PKCδ is strongly associated with infiltration of GBM cells. Notably, PKCδ 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 PKCδ 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/PKCδ/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 PKCδ signaling in GBM.",
author = "Eunji Hwang and Yoo, {Ki Chun} and Kang, {Seok Gu} and Kim, {Rae Kwon} and Cui, {Yan Hong} and Lee, {Hae June} and Kim, {Min Jung} and Lee, {Jae Seong} and Kim, {In Gyu} and Yongjoon Suh and Lee, {Su Jae}",
year = "2016",
month = "1",
day = "1",
doi = "10.18632/oncotarget.6640",
language = "English",
volume = "7",
pages = "4890--4902",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "4",

}

Hwang, E, Yoo, KC, Kang, SG, Kim, RK, Cui, YH, Lee, HJ, Kim, MJ, Lee, JS, Kim, IG, Suh, Y & Lee, SJ 2016, 'PKCδ activated by c-MET enhances infiltration of human glioblastoma cells through NOTCH2 signaling', Oncotarget, vol. 7, no. 4, pp. 4890-4902. https://doi.org/10.18632/oncotarget.6640

PKCδ activated by c-MET enhances infiltration of human glioblastoma cells through NOTCH2 signaling. / Hwang, Eunji; Yoo, Ki Chun; Kang, Seok Gu; Kim, Rae Kwon; Cui, Yan Hong; Lee, Hae June; Kim, Min Jung; Lee, Jae Seong; Kim, In Gyu; Suh, Yongjoon; Lee, Su Jae.

In: Oncotarget, Vol. 7, No. 4, 01.01.2016, p. 4890-4902.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PKCδ activated by c-MET enhances infiltration of human glioblastoma cells through NOTCH2 signaling

AU - Hwang, Eunji

AU - Yoo, Ki Chun

AU - Kang, Seok Gu

AU - Kim, Rae Kwon

AU - Cui, Yan Hong

AU - Lee, Hae June

AU - Kim, Min Jung

AU - Lee, Jae Seong

AU - Kim, In Gyu

AU - Suh, Yongjoon

AU - Lee, Su Jae

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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, PKCδ is strongly associated with infiltration of GBM cells. Notably, PKCδ 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 PKCδ 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/PKCδ/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 PKCδ signaling in GBM.

AB - 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, PKCδ is strongly associated with infiltration of GBM cells. Notably, PKCδ 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 PKCδ 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/PKCδ/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 PKCδ signaling in GBM.

UR - http://www.scopus.com/inward/record.url?scp=84958012537&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958012537&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.6640

DO - 10.18632/oncotarget.6640

M3 - Article

C2 - 26700818

AN - SCOPUS:84958012537

VL - 7

SP - 4890

EP - 4902

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 4

ER -