Cited 25 times in
An unconventional KITENIN/ErbB4-mediated downstream signal of EGF upregulates c-Jun and the invasiveness of colorectal cancer cells
DC Field | Value | Language |
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dc.contributor.author | 김호근 | - |
dc.contributor.author | 차윤진 | - |
dc.contributor.author | 홍성필 | - |
dc.date.accessioned | 2018-11-01T16:40:10Z | - |
dc.date.available | 2018-11-01T16:40:10Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/164965 | - |
dc.description.abstract | PURPOSE: 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.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.language | English | - |
dc.publisher | American Association for Cancer Research | - |
dc.relation.isPartOf | CLINICAL CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adaptor Proteins, Signal Transducing/genetics | - |
dc.subject.MESH | Adaptor Proteins, Signal Transducing/metabolism | - |
dc.subject.MESH | Antineoplastic Combined Chemotherapy Protocols/pharmacology | - |
dc.subject.MESH | Apoptosis | - |
dc.subject.MESH | Biomarkers, Tumor/genetics | - |
dc.subject.MESH | Biomarkers, Tumor/metabolism* | - |
dc.subject.MESH | Blotting, Western | - |
dc.subject.MESH | Carrier Proteins/genetics | - |
dc.subject.MESH | Carrier Proteins/metabolism* | - |
dc.subject.MESH | Cell Proliferation | - |
dc.subject.MESH | Colorectal Neoplasms/genetics | - |
dc.subject.MESH | Colorectal Neoplasms/metabolism | - |
dc.subject.MESH | Colorectal Neoplasms/pathology* | - |
dc.subject.MESH | Dishevelled Proteins | - |
dc.subject.MESH | Drug Resistance, Neoplasm/drug effects | - |
dc.subject.MESH | Epidermal Growth Factor/pharmacology | - |
dc.subject.MESH | Fluorescent Antibody Technique | - |
dc.subject.MESH | Gene Expression Regulation, Neoplastic/drug effects* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immunoenzyme Techniques | - |
dc.subject.MESH | Liver Neoplasms/genetics | - |
dc.subject.MESH | Liver Neoplasms/metabolism | - |
dc.subject.MESH | Liver Neoplasms/secondary* | - |
dc.subject.MESH | Membrane Proteins/genetics | - |
dc.subject.MESH | Membrane Proteins/metabolism* | - |
dc.subject.MESH | Neoplasm Invasiveness | - |
dc.subject.MESH | Phosphoproteins/genetics | - |
dc.subject.MESH | Phosphoproteins/metabolism | - |
dc.subject.MESH | Proto-Oncogene Proteins c-jun/genetics | - |
dc.subject.MESH | Proto-Oncogene Proteins c-jun/metabolism* | - |
dc.subject.MESH | RNA, Messenger/genetics | - |
dc.subject.MESH | Real-Time Polymerase Chain Reaction | - |
dc.subject.MESH | Receptor, Epidermal Growth Factor/genetics | - |
dc.subject.MESH | Receptor, Epidermal Growth Factor/metabolism | - |
dc.subject.MESH | Receptor, ErbB-4/genetics | - |
dc.subject.MESH | Receptor, ErbB-4/metabolism* | - |
dc.subject.MESH | Reverse Transcriptase Polymerase Chain Reaction | - |
dc.subject.MESH | Signal Transduction | - |
dc.subject.MESH | Transcription Factor AP-1/genetics | - |
dc.subject.MESH | Transcription Factor AP-1/metabolism | - |
dc.subject.MESH | Transcriptional Activation | - |
dc.subject.MESH | Tumor Cells, Cultured | - |
dc.title | An unconventional KITENIN/ErbB4-mediated downstream signal of EGF upregulates c-Jun and the invasiveness of colorectal cancer cells | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pathology (병리학교실) | - |
dc.contributor.googleauthor | Jeong A. Bae | - |
dc.contributor.googleauthor | Somy Yoon | - |
dc.contributor.googleauthor | So-Yeon Park | - |
dc.contributor.googleauthor | Jae Hyuk Lee | - |
dc.contributor.googleauthor | Jun-Eul Hwang | - |
dc.contributor.googleauthor | Hangun Kim | - |
dc.contributor.googleauthor | Young-Woo Seo | - |
dc.contributor.googleauthor | Yoon Jin Cha | - |
dc.contributor.googleauthor | Sung Pil Hong | - |
dc.contributor.googleauthor | Hoguen Kim | - |
dc.contributor.googleauthor | Ik Joo Chung | - |
dc.contributor.googleauthor | Kyung Keun Kim | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-13-2863 | - |
dc.contributor.localId | A01183 | - |
dc.contributor.localId | A04001 | - |
dc.contributor.localId | A04404 | - |
dc.relation.journalcode | J00564 | - |
dc.identifier.pmid | 24893630 | - |
dc.contributor.alternativeName | Kim, Ho Keun | - |
dc.contributor.alternativeName | Cha, Yoon Jin | - |
dc.contributor.alternativeName | Hong, Sung Pil | - |
dc.contributor.affiliatedAuthor | 김호근 | - |
dc.contributor.affiliatedAuthor | 차윤진 | - |
dc.contributor.affiliatedAuthor | 홍성필 | - |
dc.citation.volume | 20 | - |
dc.citation.number | 15 | - |
dc.citation.startPage | 4115 | - |
dc.citation.endPage | 4128 | - |
dc.identifier.bibliographicCitation | CLINICAL CANCER RESEARCH, Vol.20(15) : 4115-4128, 2014 | - |
dc.identifier.rimsid | 58288 | - |
dc.type.rims | ART | - |
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