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Protein Kinase C-delta-Mediated Recycling of Active KIT in Colon Cancer
DC Field | Value | Language |
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dc.contributor.author | Park, Misun | - |
dc.contributor.author | Kim, Won Kyu | - |
dc.contributor.author | Song, Meiying | - |
dc.contributor.author | Park, Minhee | - |
dc.contributor.author | Kim, Hyunki | - |
dc.contributor.author | Nam, Hye Jin | - |
dc.contributor.author | Baek, Sung Hee | - |
dc.contributor.author | Kim, Hoguen | - |
dc.creator | 백성희 | - |
dc.date.accessioned | 2014-05-02T00:32:46Z | - |
dc.date.available | 2014-05-02T00:32:46Z | - |
dc.date.issued | 2013-09 | - |
dc.identifier.citation | Clinical Cancer Research, Vol.19 No.18, pp. 4961-4971 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | https://hdl.handle.net/10371/91660 | - |
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-delta in the recycling of WT-KIT. We further showed that a subset of colorectal cancers exhibit expressions of both WT-KIT and activated PKC-delta 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-delta-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. (C) 2013 AACR. | en |
dc.language.iso | en | en |
dc.publisher | American Association for Cancer Research | en |
dc.subject | 자연과학 | en |
dc.title | Protein Kinase C-delta-Mediated Recycling of Active KIT in Colon Cancer | en |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 박미선 | - |
dc.contributor.AlternativeAuthor | 김원규 | - |
dc.contributor.AlternativeAuthor | 박민희 | - |
dc.contributor.AlternativeAuthor | 김현기 | - |
dc.contributor.AlternativeAuthor | 백성희 | - |
dc.contributor.AlternativeAuthor | 김호근 | - |
dc.contributor.AlternativeAuthor | 남혜진 | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-13-0131 | - |
dc.description.srnd | OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000030226/2 | - |
dc.description.srnd | SEQ:2 | - |
dc.description.srnd | PERF_CD:SNU2013-01 | - |
dc.description.srnd | EVAL_ITEM_CD:102 | - |
dc.description.srnd | USER_ID:0000030226 | - |
dc.description.srnd | ADJUST_YN:Y | - |
dc.description.srnd | EMP_ID:A076075 | - |
dc.description.srnd | DEPT_CD:3344 | - |
dc.description.srnd | CITE_RATE:7.837 | - |
dc.description.srnd | DEPT_NM:생명과학부 | - |
dc.description.srnd | SCOPUS_YN:Y | - |
dc.description.srnd | CONFIRM:Y | - |
dc.identifier.srnd | 2013-01/102/0000030226/2 | - |
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