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An unconventional KITENIN/ErbB4-mediated downstream signal of EGF upregulates c-Jun and the invasiveness of colorectal cancer cells

DC Field Value Language
dc.contributor.author김호근-
dc.contributor.author차윤진-
dc.contributor.author홍성필-
dc.date.accessioned2018-11-01T16:40:10Z-
dc.date.available2018-11-01T16:40:10Z-
dc.date.issued2014-
dc.identifier.issn1078-0432-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/164965-
dc.description.abstractPURPOSE: EGF-stimulated signaling via EGF receptor (EGFR) is important in colorectal tumorigenesis and drug targeting. However, anti-EGFR therapy is not effective in a subset of patients with colorectal cancer, suggesting that unidentified EGF-stimulated pathways might play roles in colorectal cancer. Previously, we identified KAI1 C-terminal interacting tetraspanin (KITENIN) as a metastasis-enhancing gene and found it to be highly expressed in sporadic colorectal cancer tissues. We recently found that EGF further increases KITENIN-induced elevated AP-1 activity. Here we attempted to clarify this novel EGF-stimulated molecular pathway and its roles in colorectal cancer. EXPERIMENTAL DESIGN: We analyzed how EGF modulates the downstream signaling pathway of oncogenic KITENIN in colorectal cancer cells. Biological alterations following EGF treatment were identified in KITENIN-overexpressed colorectal cancer cells with or without alteration of EGFR activity. RESULTS: We identified the KITENIN/ErbB4-Dvl2-c-Jun axis as a novel downstream signal of EGF that is switched on under elevated KITENIN conditions in an EGFR-independent manner. This unconventional EGF signal upregulates c-Jun and enhances invasion and anchorage-independent growth of colorectal cancer cells. In addition, tumor tissues from metastatic patients with colorectal cancer who showed initial poor responses to cetuximab/chemotherapy expressed higher levels of KITENIN than did responders to therapy. CONCLUSIONS: Our results highlight the role of an EGFR-independent EGF signal in mediating the invasiveness and tumorigenesis of colorectal cancer cells. This unconventional pathway might be related to the limited clinical efficacy of anti-EGFR agents in a subset of patients with colorectal cancer.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherAmerican Association for Cancer Research-
dc.relation.isPartOfCLINICAL CANCER RESEARCH-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdaptor Proteins, Signal Transducing/genetics-
dc.subject.MESHAdaptor Proteins, Signal Transducing/metabolism-
dc.subject.MESHAntineoplastic Combined Chemotherapy Protocols/pharmacology-
dc.subject.MESHApoptosis-
dc.subject.MESHBiomarkers, Tumor/genetics-
dc.subject.MESHBiomarkers, Tumor/metabolism*-
dc.subject.MESHBlotting, Western-
dc.subject.MESHCarrier Proteins/genetics-
dc.subject.MESHCarrier Proteins/metabolism*-
dc.subject.MESHCell Proliferation-
dc.subject.MESHColorectal Neoplasms/genetics-
dc.subject.MESHColorectal Neoplasms/metabolism-
dc.subject.MESHColorectal Neoplasms/pathology*-
dc.subject.MESHDishevelled Proteins-
dc.subject.MESHDrug Resistance, Neoplasm/drug effects-
dc.subject.MESHEpidermal Growth Factor/pharmacology-
dc.subject.MESHFluorescent Antibody Technique-
dc.subject.MESHGene Expression Regulation, Neoplastic/drug effects*-
dc.subject.MESHHumans-
dc.subject.MESHImmunoenzyme Techniques-
dc.subject.MESHLiver Neoplasms/genetics-
dc.subject.MESHLiver Neoplasms/metabolism-
dc.subject.MESHLiver Neoplasms/secondary*-
dc.subject.MESHMembrane Proteins/genetics-
dc.subject.MESHMembrane Proteins/metabolism*-
dc.subject.MESHNeoplasm Invasiveness-
dc.subject.MESHPhosphoproteins/genetics-
dc.subject.MESHPhosphoproteins/metabolism-
dc.subject.MESHProto-Oncogene Proteins c-jun/genetics-
dc.subject.MESHProto-Oncogene Proteins c-jun/metabolism*-
dc.subject.MESHRNA, Messenger/genetics-
dc.subject.MESHReal-Time Polymerase Chain Reaction-
dc.subject.MESHReceptor, Epidermal Growth Factor/genetics-
dc.subject.MESHReceptor, Epidermal Growth Factor/metabolism-
dc.subject.MESHReceptor, ErbB-4/genetics-
dc.subject.MESHReceptor, ErbB-4/metabolism*-
dc.subject.MESHReverse Transcriptase Polymerase Chain Reaction-
dc.subject.MESHSignal Transduction-
dc.subject.MESHTranscription Factor AP-1/genetics-
dc.subject.MESHTranscription Factor AP-1/metabolism-
dc.subject.MESHTranscriptional Activation-
dc.subject.MESHTumor Cells, Cultured-
dc.titleAn unconventional KITENIN/ErbB4-mediated downstream signal of EGF upregulates c-Jun and the invasiveness of colorectal cancer cells-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pathology (병리학교실)-
dc.contributor.googleauthorJeong A. Bae-
dc.contributor.googleauthorSomy Yoon-
dc.contributor.googleauthorSo-Yeon Park-
dc.contributor.googleauthorJae Hyuk Lee-
dc.contributor.googleauthorJun-Eul Hwang-
dc.contributor.googleauthorHangun Kim-
dc.contributor.googleauthorYoung-Woo Seo-
dc.contributor.googleauthorYoon Jin Cha-
dc.contributor.googleauthorSung Pil Hong-
dc.contributor.googleauthorHoguen Kim-
dc.contributor.googleauthorIk Joo Chung-
dc.contributor.googleauthorKyung Keun Kim-
dc.identifier.doi10.1158/1078-0432.CCR-13-2863-
dc.contributor.localIdA01183-
dc.contributor.localIdA04001-
dc.contributor.localIdA04404-
dc.relation.journalcodeJ00564-
dc.identifier.pmid24893630-
dc.contributor.alternativeNameKim, Ho Keun-
dc.contributor.alternativeNameCha, Yoon Jin-
dc.contributor.alternativeNameHong, Sung Pil-
dc.contributor.affiliatedAuthor김호근-
dc.contributor.affiliatedAuthor차윤진-
dc.contributor.affiliatedAuthor홍성필-
dc.citation.volume20-
dc.citation.number15-
dc.citation.startPage4115-
dc.citation.endPage4128-
dc.identifier.bibliographicCitationCLINICAL CANCER RESEARCH, Vol.20(15) : 4115-4128, 2014-
dc.identifier.rimsid58288-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers

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