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

DC FieldValueLanguage
dc.contributor.author강석구-
dc.date.accessioned2017-02-24T11:06:52Z-
dc.date.available2017-02-24T11:06:52Z-
dc.date.issued2016-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/146649-
dc.description.abstractPoor 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.-
dc.description.statementOfResponsibilityopen-
dc.format.extent4890~4902-
dc.languageEnglish-
dc.publisherImpact Journals-
dc.relation.isPartOfONCOTARGET-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAged-
dc.subject.MESHAnimals-
dc.subject.MESHApoptosis-
dc.subject.MESHBiomarkers, Tumor/genetics-
dc.subject.MESHBiomarkers, Tumor/metabolism*-
dc.subject.MESHBlotting, Western-
dc.subject.MESHCell Movement-
dc.subject.MESHCell Proliferation-
dc.subject.MESHFemale-
dc.subject.MESHGlioblastoma/genetics-
dc.subject.MESHGlioblastoma/metabolism-
dc.subject.MESHGlioblastoma/pathology*-
dc.subject.MESHHumans-
dc.subject.MESHImmunoenzyme Techniques-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred BALB C-
dc.subject.MESHMice, Nude-
dc.subject.MESHProtein Kinase C-delta/genetics-
dc.subject.MESHProtein Kinase C-delta/metabolism*-
dc.subject.MESHProto-Oncogene Proteins c-met/genetics-
dc.subject.MESHProto-Oncogene Proteins c-met/metabolism*-
dc.subject.MESHRNA, Messenger/genetics-
dc.subject.MESHReal-Time Polymerase Chain Reaction-
dc.subject.MESHReceptor, Notch2/genetics-
dc.subject.MESHReceptor, Notch2/metabolism*-
dc.subject.MESHReverse Transcriptase Polymerase Chain Reaction-
dc.subject.MESHTumor Cells, Cultured-
dc.subject.MESHXenograft Model Antitumor Assays-
dc.titlePKCδ activated by c-MET enhances infiltration of human glioblastoma cells through NOTCH2 signaling-
dc.typeArticle-
dc.publisher.locationUnited States-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Neurosurgery-
dc.contributor.googleauthorEunji Hwang-
dc.contributor.googleauthorKi-Chun Yoo-
dc.contributor.googleauthorSeok-Gu Kang-
dc.contributor.googleauthorRae-Kwon Kim-
dc.contributor.googleauthorYan-Hong Cui-
dc.contributor.googleauthorHae-June Lee-
dc.contributor.googleauthorMin-Jung Kim-
dc.contributor.googleauthorJae-Seong Lee-
dc.contributor.googleauthorIn-Gyu Kim-
dc.contributor.googleauthorYongjoon Suh-
dc.contributor.googleauthorSu-Jae Lee-
dc.identifier.doi10.18632/oncotarget.6640-
dc.contributor.localIdA00036-
dc.relation.journalcodeJ02421-
dc.identifier.eissn1949-2553-
dc.identifier.pmid26700818-
dc.subject.keywordNOTCH2-
dc.subject.keywordPKCδ-
dc.subject.keywordc-MET-
dc.subject.keywordglioblastoma-
dc.subject.keywordinfiltration-
dc.contributor.alternativeNameKang, Seok Gu-
dc.contributor.affiliatedAuthorKang, Seok Gu-
dc.citation.volume7-
dc.citation.number4-
dc.citation.startPage4890-
dc.citation.endPage4902-
dc.identifier.bibliographicCitationONCOTARGET , Vol.7(4) : 4890-4902, 2016-
dc.date.modified2017-02-24-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers

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