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Identification of a novel cell death receptor mediating IGFBP-3-induced anti-tumor effects in breast and prostate cancer
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김호성 | - |
dc.date.accessioned | 2015-04-23T17:25:12Z | - |
dc.date.available | 2015-04-23T17:25:12Z | - |
dc.date.issued | 2010 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/102428 | - |
dc.description.abstract | Insulin-like growth factor-binding protein-3 (IGFBP-3), a major regulator of endocrine actions of IGFs, is a p53-regulated potent apoptotic factor and is significantly suppressed in a variety of cancers. Recent epidemiologic studies suggest that IGFBP-3 contributes to cancer risk protection in a variety of cancers, and a polymorphic variation of IGFBP-3 influences cancer risk, although other studies vary in their conclusions. Some antiproliferative actions of IGFBP-3 have been reported to be independent of IGFs, but the precise biochemical/molecular mechanisms of IGF-independent, antiproliferative actions of IGFBP-3 are largely unknown. Here we report a new cell death receptor, IGFBP-3R, that is a single-span membrane protein and binds specifically to IGFBP-3 but not other IGFBP species. Expression analysis of IGFBP-3 and IGFBP-3R indicates that the IGFBP-3/IGFBP-3R axis is impaired in breast and prostate cancer. We also provide evidence for anti-tumor effect of IGFBP-3R in vivo using prostate and breast cancer xenografts in athymic nude mice. Further in vitro studies demonstrate that IGFBP-3R mediates IGFBP-3-induced caspase-8-dependent apoptosis in various cancer cells. Knockdown of IGFBP-3R attenuated IGFBP-3-induced caspase activities and apoptosis, whereas overexpression of IGFBP-3R enhanced IGFBP-3 biological effects. IGFBP-3R physically interacts and activates caspase-8, and knockdown of caspase-8 expression or activity inhibited IGFBP-3/IGFBP-3R-induced apoptosis. Here, we propose that IGFBP-3R represents a novel cell death receptor and is essential for the IGFBP-3-induced apoptosis and tumor suppression. Thus, the IGFBP-3/IGFBP-3R axis may provide therapeutic and prognostic value for the treatment of cancer | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 30233~30246 | - |
dc.relation.isPartOf | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Apoptosis* | - |
dc.subject.MESH | Base Sequence | - |
dc.subject.MESH | Breast Neoplasms/genetics | - |
dc.subject.MESH | Breast Neoplasms/metabolism* | - |
dc.subject.MESH | Breast Neoplasms/pathology | - |
dc.subject.MESH | Caspase 8/genetics | - |
dc.subject.MESH | Caspase 8/metabolism | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Gene Expression Regulation, Neoplastic/genetics | - |
dc.subject.MESH | Gene Knockdown Techniques | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Insulin-Like Growth Factor Binding Protein 3 | - |
dc.subject.MESH | Insulin-Like Growth Factor Binding Proteins/genetics | - |
dc.subject.MESH | Insulin-Like Growth Factor Binding Proteins/metabolism* | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Membrane Proteins/genetics | - |
dc.subject.MESH | Membrane Proteins/metabolism* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Nude | - |
dc.subject.MESH | Molecular Sequence Data | - |
dc.subject.MESH | Neoplasm Proteins/genetics | - |
dc.subject.MESH | Neoplasm Proteins/metabolism* | - |
dc.subject.MESH | Neoplasm Transplantation | - |
dc.subject.MESH | Prostatic Neoplasms/genetics | - |
dc.subject.MESH | Prostatic Neoplasms/metabolism* | - |
dc.subject.MESH | Prostatic Neoplasms/pathology | - |
dc.subject.MESH | Receptors, Cell Surface/genetics | - |
dc.subject.MESH | Receptors, Cell Surface/metabolism* | - |
dc.subject.MESH | Transplantation, Heterologous | - |
dc.title | Identification of a novel cell death receptor mediating IGFBP-3-induced anti-tumor effects in breast and prostate cancer | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pediatrics (소아과학) | - |
dc.contributor.googleauthor | Angela R. Ingermann | - |
dc.contributor.googleauthor | Yong-Feng Yang | - |
dc.contributor.googleauthor | Jinfeng Han | - |
dc.contributor.googleauthor | Aki Mikami | - |
dc.contributor.googleauthor | Ama E. Garza | - |
dc.contributor.googleauthor | Lathika Mohanraj | - |
dc.contributor.googleauthor | Lingbo Fan | - |
dc.contributor.googleauthor | Michael Idowu | - |
dc.contributor.googleauthor | Joy L. Ware | - |
dc.contributor.googleauthor | Ho-Seong Kim | - |
dc.contributor.googleauthor | Dae-Yeol Lee | - |
dc.contributor.googleauthor | Youngman Oh | - |
dc.identifier.doi | 10.1074/jbc.M110.122226 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01184 | - |
dc.relation.journalcode | J01258 | - |
dc.identifier.eissn | 1083-351X | - |
dc.identifier.pmid | 20353938 | - |
dc.contributor.alternativeName | Kim, Ho Seong | - |
dc.contributor.affiliatedAuthor | Kim, Ho Seong | - |
dc.citation.volume | 285 | - |
dc.citation.number | 39 | - |
dc.citation.startPage | 30233 | - |
dc.citation.endPage | 30246 | - |
dc.identifier.bibliographicCitation | JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.285(39) : 30233-30246, 2010 | - |
dc.identifier.rimsid | 57324 | - |
dc.type.rims | ART | - |
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