Please use this identifier to cite or link to this item: https://doi.org/10.1158/1535-7163.MCT-16-0739
DC FieldValue
dc.titlePPARγ Ligand-induced Annexin A1 Expression Determines Chemotherapy Response via Deubiquitination of Death Domain Kinase RIP in Triple-negative Breast Cancers.
dc.contributor.authorChen, Luxi
dc.contributor.authorYuan, Yi
dc.contributor.authorKar, Shreya
dc.contributor.authorKanchi, Madhu M
dc.contributor.authorArora, Suruchi
dc.contributor.authorKim, Ji E
dc.contributor.authorKoh, Pei F
dc.contributor.authorYousef, Einas
dc.contributor.authorSamy, Ramar P
dc.contributor.authorShanmugam, Muthu K
dc.contributor.authorTuan Z
dc.contributor.authorShin, Sung W
dc.contributor.authorArfuso, Frank
dc.contributor.authorShen, Han M
dc.contributor.authorYang, Henry
dc.contributor.authorGoh, Boon C
dc.contributor.authorPark, Joo I
dc.contributor.authorGaboury, Louis
dc.contributor.authorLobie, Peter E
dc.contributor.authorSethi, Gautam
dc.contributor.authorLim, Lina HK
dc.contributor.authorKumar, Alan P
dc.date.accessioned2020-09-28T06:02:04Z
dc.date.available2020-09-28T06:02:04Z
dc.date.issued2017-11
dc.identifier.citationChen, Luxi, Yuan, Yi, Kar, Shreya, Kanchi, Madhu M, Arora, Suruchi, Kim, Ji E, Koh, Pei F, Yousef, Einas, Samy, Ramar P, Shanmugam, Muthu K, Tuan Z, Shin, Sung W, Arfuso, Frank, Shen, Han M, Yang, Henry, Goh, Boon C, Park, Joo I, Gaboury, Louis, Lobie, Peter E, Sethi, Gautam, Lim, Lina HK, Kumar, Alan P (2017-11). PPARγ Ligand-induced Annexin A1 Expression Determines Chemotherapy Response via Deubiquitination of Death Domain Kinase RIP in Triple-negative Breast Cancers.. Mol Cancer Ther 16 (11) : 2528-2542. ScholarBank@NUS Repository. https://doi.org/10.1158/1535-7163.MCT-16-0739
dc.identifier.issn15357163
dc.identifier.issn15388514
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/176793
dc.description.abstractMetastatic breast cancer is still incurable so far; new specifically targeted and more effective therapies for triple-negative breast cancer (TNBC) are required in the clinic. In this study, our clinical data have established that basal and claudin-low subtypes of breast cancer (TNBC types) express significantly higher levels of Annexin A1 (ANXA1) with poor survival outcomes. Using human cancer cell lines that model the TNBC subtype, we observed a strong positive correlation between expression of ANXA1 and PPARγ. A similar correlation between these two markers was also established in our clinical breast cancer patients' specimens. To establish a link between these two markers in TNBC, we show de novo expression of ANXA1 is induced by activation of PPARγ both in vitro and in vivo and it has a predictive value in determining chemosensitivity to PPARγ ligands. Mechanistically, we show for the first time PPARγ-induced ANXA1 protein directly interacts with receptor interacting protein-1 (RIP1), promoting its deubiquitination and thereby activating the caspase-8-dependent death pathway. We further identified this underlying mechanism also involved a PPARγ-induced ANXA1-dependent autoubiquitination of cIAP1, the direct E3 ligase of RIP1, shifting cIAP1 toward proteosomal degradation. Collectively, our study provides first insight for the suitability of using drug-induced expression of ANXA1 as a new player in RIP1-induced death machinery in TNBCs, presenting itself both as an inclusion criterion for patient selection and surrogate marker for drug response in future PPARγ chemotherapy trials. Mol Cancer Ther; 16(11); 2528-42. ©2017 AACR.
dc.sourceElements
dc.subjectAnimals
dc.subjectAnnexin A1
dc.subjectCaspase 8
dc.subjectCell Proliferation
dc.subjectDeath Domain
dc.subjectDeubiquitinating Enzymes
dc.subjectDrug Resistance, Neoplasm
dc.subjectFemale
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectHumans
dc.subjectInhibitor of Apoptosis Proteins
dc.subjectLigands
dc.subjectMCF-7 Cells
dc.subjectMice
dc.subjectNeoplasm Metastasis
dc.subjectNuclear Pore Complex Proteins
dc.subjectPPAR gamma
dc.subjectRNA-Binding Proteins
dc.subjectTriple Negative Breast Neoplasms
dc.subjectXenograft Model Antitumor Assays
dc.typeArticle
dc.date.updated2020-09-28T01:19:25Z
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.description.doi10.1158/1535-7163.MCT-16-0739
dc.description.sourcetitleMol Cancer Ther
dc.description.volume16
dc.description.issue11
dc.description.page2528-2542
dc.published.statePublished
Appears in Collections:Staff Publications
Elements

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
2017 Chen MCT.pdfAccepted version3.39 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

16
checked on Mar 3, 2021

Page view(s)

51
checked on Feb 26, 2021

Download(s)

2
checked on Feb 26, 2021

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.