Cited 19 times in
Protein Kinase C-δ–Mediated Recycling of Active KIT in Colon Cancer
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김원규 | - |
dc.contributor.author | 김현기 | - |
dc.contributor.author | 김호근 | - |
dc.contributor.author | 박미선 | - |
dc.contributor.author | 박민희 | - |
dc.contributor.author | 송미영 | - |
dc.date.accessioned | 2014-12-18T09:08:12Z | - |
dc.date.available | 2014-12-18T09:08:12Z | - |
dc.date.issued | 2013 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/87602 | - |
dc.description.abstract | PURPOSE: Abnormal signaling through receptor tyrosine kinase (RTK) moieties is important in tumorigenesis and drug targeting of colorectal cancers. Wild-type KIT (WT-KIT), a RTK that is activated upon binding with stem cell factor (SCF), is highly expressed in some colon cancers; however, little is known about the functional role of SCF-dependent KIT activation in colon cancer pathogenesis. We aimed to elucidate the conditions and roles of WT-KIT activation in colon cancer tumorigenesis. EXPERIMENTAL DESIGN: Colorectal cancers with KIT expression were characterized by immunoblotting and immunohistochemistry. The biologic alterations after KIT-SCF binding were analyzed with or without protein kinase C (PKC) activation. RESULTS: We found that WT-KIT was expressed in a subset of colon cancer cell lines and was activated by SCF, leading to activation of downstream AKT and extracellular signal-regulated kinase (ERK) signaling pathways. We also showed that KIT expression gradually decreased, after prolonged SCF stimulation, due to lysosomal degradation. Degradation of WT-KIT after SCF binding was significantly rescued when PKC was activated. We also showed the involvement of activated PKC-δ in the recycling of WT-KIT. We further showed that a subset of colorectal cancers exhibit expressions of both WT-KIT and activated PKC-δ and that expression of KIT is correlated with poor patient survival (P = 0.004). CONCLUSIONS: Continuous downstream signal activation after KIT-SCF binding is accomplished through PKC-δ-mediated recycling of KIT. This sustained KIT activation may contribute to tumor progression in a subset of colon cancers with KIT expression and might provide the rationale for a therapeutic approach targeting KIT. | - |
dc.description.statementOfResponsibility | open | - |
dc.relation.isPartOf | CLINICAL CANCER RESEARCH | - |
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 | Apoptosis | - |
dc.subject.MESH | Blotting, Western | - |
dc.subject.MESH | Cell Adhesion | - |
dc.subject.MESH | Cell Movement* | - |
dc.subject.MESH | Cell Proliferation* | - |
dc.subject.MESH | Colorectal Neoplasms/metabolism* | - |
dc.subject.MESH | Colorectal Neoplasms/mortality | - |
dc.subject.MESH | Colorectal Neoplasms/pathology* | - |
dc.subject.MESH | Disease Progression | - |
dc.subject.MESH | Extracellular Signal-Regulated MAP Kinases/genetics | - |
dc.subject.MESH | Extracellular Signal-Regulated MAP Kinases/metabolism | - |
dc.subject.MESH | Fluorescent Antibody Technique | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immunoenzyme Techniques | - |
dc.subject.MESH | Immunoprecipitation | - |
dc.subject.MESH | Lysosomes/metabolism | - |
dc.subject.MESH | Neoplasm Staging | - |
dc.subject.MESH | Phosphatidylinositol 3-Kinases/genetics | - |
dc.subject.MESH | Phosphatidylinositol 3-Kinases/metabolism | - |
dc.subject.MESH | Prognosis | - |
dc.subject.MESH | Protein Kinase C-delta/genetics | - |
dc.subject.MESH | Protein Kinase C-delta/metabolism* | - |
dc.subject.MESH | Proto-Oncogene Proteins c-kit/genetics | - |
dc.subject.MESH | Proto-Oncogene Proteins c-kit/metabolism* | - |
dc.subject.MESH | RNA, Messenger/genetics | - |
dc.subject.MESH | Real-Time Polymerase Chain Reaction | - |
dc.subject.MESH | Reverse Transcriptase Polymerase Chain Reaction | - |
dc.subject.MESH | Stem Cell Factor/genetics | - |
dc.subject.MESH | Stem Cell Factor/metabolism | - |
dc.subject.MESH | Survival Rate | - |
dc.subject.MESH | Tissue Array Analysis | - |
dc.subject.MESH | Tumor Cells, Cultured | - |
dc.title | Protein Kinase C-δ–Mediated Recycling of Active KIT in Colon Cancer | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pathology (병리학) | - |
dc.contributor.googleauthor | Misun Park | - |
dc.contributor.googleauthor | Won Kyu Kim | - |
dc.contributor.googleauthor | Meiying Song | - |
dc.contributor.googleauthor | Minhee Park | - |
dc.contributor.googleauthor | Hyunki Kim | - |
dc.contributor.googleauthor | Hye Jin Nam | - |
dc.contributor.googleauthor | Sung Hee Baek | - |
dc.contributor.googleauthor | Hoguen Kim | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-13-0131 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00764 | - |
dc.contributor.localId | A01108 | - |
dc.contributor.localId | A01183 | - |
dc.contributor.localId | A01461 | - |
dc.contributor.localId | A01471 | - |
dc.contributor.localId | A02021 | - |
dc.relation.journalcode | J00564 | - |
dc.identifier.pmid | 23881925 | - |
dc.identifier.url | http://clincancerres.aacrjournals.org/content/19/18/4961.long | - |
dc.subject.keyword | Apoptosis | - |
dc.subject.keyword | Blotting, Western | - |
dc.subject.keyword | Cell Adhesion | - |
dc.subject.keyword | Cell Movement* | - |
dc.subject.keyword | Cell Proliferation* | - |
dc.subject.keyword | Colorectal Neoplasms/metabolism* | - |
dc.subject.keyword | Colorectal Neoplasms/mortality | - |
dc.subject.keyword | Colorectal Neoplasms/pathology* | - |
dc.subject.keyword | Disease Progression | - |
dc.subject.keyword | Extracellular Signal-Regulated MAP Kinases/genetics | - |
dc.subject.keyword | Extracellular Signal-Regulated MAP Kinases/metabolism | - |
dc.subject.keyword | Fluorescent Antibody Technique | - |
dc.subject.keyword | Humans | - |
dc.subject.keyword | Immunoenzyme Techniques | - |
dc.subject.keyword | Immunoprecipitation | - |
dc.subject.keyword | Lysosomes/metabolism | - |
dc.subject.keyword | Neoplasm Staging | - |
dc.subject.keyword | Phosphatidylinositol 3-Kinases/genetics | - |
dc.subject.keyword | Phosphatidylinositol 3-Kinases/metabolism | - |
dc.subject.keyword | Prognosis | - |
dc.subject.keyword | Protein Kinase C-delta/genetics | - |
dc.subject.keyword | Protein Kinase C-delta/metabolism* | - |
dc.subject.keyword | Proto-Oncogene Proteins c-kit/genetics | - |
dc.subject.keyword | Proto-Oncogene Proteins c-kit/metabolism* | - |
dc.subject.keyword | RNA, Messenger/genetics | - |
dc.subject.keyword | Real-Time Polymerase Chain Reaction | - |
dc.subject.keyword | Reverse Transcriptase Polymerase Chain Reaction | - |
dc.subject.keyword | Stem Cell Factor/genetics | - |
dc.subject.keyword | Stem Cell Factor/metabolism | - |
dc.subject.keyword | Survival Rate | - |
dc.subject.keyword | Tissue Array Analysis | - |
dc.subject.keyword | Tumor Cells, Cultured | - |
dc.contributor.alternativeName | Kim, Won Kyu | - |
dc.contributor.alternativeName | Kim, Hyun Ki | - |
dc.contributor.alternativeName | Kim, Ho Keun | - |
dc.contributor.alternativeName | Park, Mi Sun | - |
dc.contributor.alternativeName | Park, Min Hee | - |
dc.contributor.alternativeName | Song, Mei Ying | - |
dc.contributor.affiliatedAuthor | Kim, Won Kyu | - |
dc.contributor.affiliatedAuthor | Kim, Hyun Ki | - |
dc.contributor.affiliatedAuthor | Kim, Ho Keun | - |
dc.contributor.affiliatedAuthor | Park, Mi Sun | - |
dc.contributor.affiliatedAuthor | Park, Min Hee | - |
dc.contributor.affiliatedAuthor | Song, Mei Ying | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 19 | - |
dc.citation.number | 18 | - |
dc.citation.startPage | 4961 | - |
dc.citation.endPage | 4971 | - |
dc.identifier.bibliographicCitation | CLINICAL CANCER RESEARCH, Vol.19(18) : 4961-4971, 2013 | - |
dc.identifier.rimsid | 34340 | - |
dc.type.rims | ART | - |
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