Chemosensitivity to HM90822, a novel synthetic IAP antagonist, is determined by p-AKT-inducible XIAP phosphorylation in human pancreatic cancer cells

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dc.contributor.authorS W Hong-
dc.contributor.authorJ S Shin-
dc.contributor.authorJ H Moon-
dc.contributor.authorS A Jung-
dc.contributor.authorD I Koh-
dc.contributor.authorY Ryu-
dc.contributor.authorY S Park-
dc.contributor.authorD Y Kim-
dc.contributor.authorS S Park-
dc.contributor.authorJ K Hong-
dc.contributor.authorE H Kim-
dc.contributor.authorM J Kim-
dc.contributor.authorH R Jeong-
dc.contributor.authorI H Bae-
dc.contributor.authorY G Ahn-
dc.contributor.authorK H Suh-
dc.contributor.authorI J Cho-
dc.contributor.authorJong Soon Kang-
dc.contributor.authorY S Hong-
dc.contributor.authorJ S Lee-
dc.contributor.authorD H Jin-
dc.contributor.authorT W Kim-
dc.date.accessioned2020-11-05T12:59:40Z-
dc.date.available2020-11-05T12:59:40Z-
dc.date.issued2020-
dc.identifier.issn01676997-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/23180-
dc.description.abstractInhibitor of apoptosis proteins (IAPs) are overexpressed in the majority of cancers and prevent apoptosis by inhibiting caspases. IAPs have therefore attracted considerable attention as potential targets for anticancer therapy. Here, we demonstrated that HM90822 (abbreviated HM822; a new synthetic IAP antagonist) induced apoptotic cell death via proteasome-dependent degradation of BIR2/3 domain-containing IAPs in human pancreatic cancer cells. HM822 inhibited the expression of XIAP and cIAP1/2 proteins in Panc-1 and BxPC-3 cells, which are sensitive to HM822. HM822 also induced IAP ubiquitination and promoted proteasome-dependent IAP degradation. However, cells expressing phospho-XIAP (Ser87) and AKT exhibited resistance to HM822. In other words, the overexpression of AKT-CA (constitutive active form for AKT) or AKT-WT induced resistance to HM822. In addition, in Panc-1 xenograft and orthotopic mouse models, we revealed that tumor growth was suppressed by the administration of HM822. Taken together, these results suggest that HM822 induces apoptosis through ubiquitin/proteasome-dependent degradation of BIR3 domain-containing IAPs. These findings suggest that phospho-XIAP and phospho-AKT may be used as biomarkers for predicting the efficacy of HM822 in pancreatic cancer patients.-
dc.publisherSpringer-
dc.titleChemosensitivity to HM90822, a novel synthetic IAP antagonist, is determined by p-AKT-inducible XIAP phosphorylation in human pancreatic cancer cells-
dc.title.alternativeChemosensitivity to HM90822, a novel synthetic IAP antagonist, is determined by p-AKT-inducible XIAP phosphorylation in human pancreatic cancer cells-
dc.typeArticle-
dc.citation.titleInvestigational New Drugs-
dc.citation.number6-
dc.citation.endPage1706-
dc.citation.startPage1696-
dc.citation.volume38-
dc.contributor.affiliatedAuthorJong Soon Kang-
dc.contributor.alternativeName홍승우-
dc.contributor.alternativeName신재식-
dc.contributor.alternativeName문재희-
dc.contributor.alternativeName정수아-
dc.contributor.alternativeName고동인-
dc.contributor.alternativeName유예성-
dc.contributor.alternativeName박윤선-
dc.contributor.alternativeName김도연-
dc.contributor.alternativeName박상수-
dc.contributor.alternativeName홍준기-
dc.contributor.alternativeName김은호-
dc.contributor.alternativeName김미진-
dc.contributor.alternativeName정홍래-
dc.contributor.alternativeName배인환-
dc.contributor.alternativeName안영길-
dc.contributor.alternativeName서귀현-
dc.contributor.alternativeName조익준-
dc.contributor.alternativeName강종순-
dc.contributor.alternativeName홍용상-
dc.contributor.alternativeName이정신-
dc.contributor.alternativeName진동훈-
dc.contributor.alternativeName김태원-
dc.identifier.bibliographicCitationInvestigational New Drugs, vol. 38, no. 6, pp. 1696-1706-
dc.identifier.doi10.1007/s10637-020-00956-9-
dc.subject.keywordIAPs-
dc.subject.keywordHM90822 (HM822)-
dc.subject.keywordubiquitination-
dc.subject.keywordapoptosis-
dc.subject.keywordpancreatic cancer-
dc.subject.localIAPs-
dc.subject.localIAP-
dc.subject.localHM90822 (HM822)-
dc.subject.localubiquitination-
dc.subject.localUbiquitination-
dc.subject.localapoptosis-
dc.subject.localApoptosis-
dc.subject.localpancreatic cancer-
dc.subject.localPancreatic cancer-
dc.description.journalClassY-
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Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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