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Coupling of LETM1 up-regulation with oxidative phosphorylation and platelet-derived growth factor receptor signaling via YAP1 transactivation

DC Field Value Language
dc.contributor.author김다함-
dc.contributor.author이슬기-
dc.contributor.author이은직-
dc.contributor.author이잔디-
dc.contributor.author정웅윤-
dc.contributor.author조영석-
dc.contributor.author이우경-
dc.date.accessioned2017-10-26T07:34:08Z-
dc.date.available2017-10-26T07:34:08Z-
dc.date.issued2016-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/152202-
dc.description.abstractPersistent cellular proliferation and metabolic reprogramming are essential processes in carcinogenesis. Here, we performed Gene Set Enrichment Analysis (GSEA) and found that that LETM1, a mitochondrial calcium transporter, is associated with cellular growth signals such as platelet-derived growth factor (PDGF) receptor signaling and insulin signaling pathways. These results were then verified by qRT-PCR and immnunoblotting. Mechanistically, up-regulation of LETM1 induced YAP1 nuclear accumulation, increasing the expression of PDGFB, PDGFRB and THBS4. Consistent with this, LETM1 silencing caused loss of YAP1 nuclear signal, decreasing the expression of PDGFB, PDGFRB and THBS4. Immunohistochemical staining consistently indicated a positive association between LETM1 up-regulation, YAP1 nuclear localization and high PDGFB expression. In clinical data analysis, LETM1 up-regulation in thyroid cancer was found to be related to aggressive tumor features such as lymphovascular invasion (LVI, P < 0.001) and lymph node metastasis (LNM, P = 0.011). Multivariate analysis demonstrated that LETM1 up-regulation increases the risk of LVI and LNM (OR = 3.455, 95% CI = 1.537-7.766 and OR = 3.043, 95% CI = 1.282-7.225, respectively). Collectively, these data suggest that up-regulation of LETM1 induces sustained activation of proliferative signaling pathways, such as PDGF signal pathway by AKT induced YAP1 transactivation, resulting in aggressive thyroid cancer phenotypes.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherImpact Journals-
dc.relation.isPartOfONCOTARGET-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://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.MESHAdult-
dc.subject.MESHCalcium-Binding Proteins/genetics-
dc.subject.MESHCalcium-Binding Proteins/metabolism*-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHFemale-
dc.subject.MESHGene Expression Regulation, Neoplastic-
dc.subject.MESHHumans-
dc.subject.MESHMale-
dc.subject.MESHMembrane Proteins/genetics-
dc.subject.MESHMembrane Proteins/metabolism*-
dc.subject.MESHMiddle Aged-
dc.subject.MESHOxidative Phosphorylation*-
dc.subject.MESHPhosphoproteins/genetics-
dc.subject.MESHPhosphoproteins/metabolism*-
dc.subject.MESHRNA Interference-
dc.subject.MESHReceptor, Platelet-Derived Growth Factor beta/genetics-
dc.subject.MESHReceptor, Platelet-Derived Growth Factor beta/metabolism*-
dc.subject.MESHThyroid Neoplasms/genetics-
dc.subject.MESHThyroid Neoplasms/metabolism-
dc.subject.MESHThyroid Neoplasms/pathology-
dc.subject.MESHTranscriptional Activation-
dc.subject.MESHUp-Regulation*-
dc.titleCoupling of LETM1 up-regulation with oxidative phosphorylation and platelet-derived growth factor receptor signaling via YAP1 transactivation-
dc.typeArticle-
dc.publisher.locationUnited States-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Internal Medicine-
dc.contributor.googleauthorJandee Lee-
dc.contributor.googleauthorWoo Kyung Lee-
dc.contributor.googleauthorMi-Youn Seol-
dc.contributor.googleauthorSeul Gi Lee-
dc.contributor.googleauthorDaham Kim-
dc.contributor.googleauthorHyunji Kim-
dc.contributor.googleauthorJongsun Park-
dc.contributor.googleauthorSang Geun Jung-
dc.contributor.googleauthorWoong Youn Chung-
dc.contributor.googleauthorEun Jig Lee-
dc.contributor.googleauthorYoung Suk Jo-
dc.identifier.doi10.18632/oncotarget.11456-
dc.contributor.localIdA04626-
dc.contributor.localIdA03050-
dc.contributor.localIdA03066-
dc.contributor.localIdA03674-
dc.contributor.localIdA03853-
dc.contributor.localIdA00363-
dc.contributor.localIdA02991-
dc.relation.journalcodeJ02421-
dc.identifier.eissn1949-2553-
dc.identifier.pmid27556512-
dc.subject.keywordLETM1-
dc.subject.keywordcell proliferation-
dc.subject.keywordelectron transport chain-
dc.subject.keywordmetabolism-
dc.subject.keywordprognosis-
dc.contributor.alternativeNameKim, Da Ham-
dc.contributor.alternativeNameLee, Seul Gi-
dc.contributor.alternativeNameLee, Eun Jig-
dc.contributor.alternativeNameLee, Jan Dee-
dc.contributor.alternativeNameChung, Woung Youn-
dc.contributor.alternativeNameJo, Young Suk-
dc.contributor.affiliatedAuthorLee, Seul Gi-
dc.contributor.affiliatedAuthorLee, Eun Jig-
dc.contributor.affiliatedAuthorLee, Jan Dee-
dc.contributor.affiliatedAuthorChung, Woung Youn-
dc.contributor.affiliatedAuthorJo, Young Suk-
dc.contributor.affiliatedAuthorKim, Da Ham-
dc.citation.volume7-
dc.citation.number41-
dc.citation.startPage66728-
dc.citation.endPage66739-
dc.identifier.bibliographicCitationONCOTARGET , Vol.7(41) : 66728-66739, 2016-
dc.date.modified2017-10-24-
dc.identifier.rimsid46979-
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 Surgery (외과학교실) > 1. Journal Papers

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