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Critical and reciprocal regulation of KLF4 and SLUG in transforming growth factor β-initiated prostate cancer epithelial-mesenchymal transition

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dc.contributor.author Liu Y.-N.
dc.contributor.author Abou-Kheir W.
dc.contributor.author Yin J.J.
dc.contributor.author Fang L.
dc.contributor.author Hynes P.
dc.contributor.author Casey O.
dc.contributor.author Hu D.
dc.contributor.author Wan Y.
dc.contributor.author Seng V.
dc.contributor.author Sheppard-Tillman H.
dc.contributor.author Martin P.
dc.contributor.author Kelly K.
dc.contributor.editor
dc.date Mar-2012
dc.date.accessioned 2017-09-07T06:59:59Z
dc.date.available 2017-09-07T06:59:59Z
dc.date.issued 2012
dc.identifier 10.1128/MCB.06306-11
dc.identifier.isbn
dc.identifier.issn 02707306
dc.identifier.uri http://hdl.handle.net/10938/11225
dc.description.abstract Epithelial-mesenchymal transition (EMT) is implicated in various pathological processes within the prostate, including benign prostate hyperplasia (BPH) and prostate cancer progression. However, an ordered sequence of signaling events initiating carcinoma-associated EMT has not been established. In a model of transforming growth factorβ (TGFβ)-induced prostatic EMT, SLUG is the dominant regulator of EMT initiation in vitro and in vivo, as demonstrated by the inhibition of EMT following Slug depletion. In contrast, SNAIL depletion was significantly less rate limiting. TGFβ-stimulated KLF4 degradation is required for SLUG induction. Expression of a degradation-resistant KLF4 mutant inhibited EMT, and furthermore, depletion of Klf4 was sufficient to initiate SLUG-dependent EMT. We show that KLF4 and another epithelial determinant, FOXA1, are direct transcriptional inhibitors of SLUG expression in mouse and human prostate cancer cells. Furthermore, self-reinforcing regulatory loops for SLUG-KLF4 and SLUG-FOXA1 lead to SLUG-dependent binding of polycomb repressive complexes to the Klf4 and Foxa1 promoters, silencing transcription and consolidating mesenchymal commitment. Analysis of tissue arrays demonstrated decreased KLF4 and increased SLUG expression in advanced-stage primary prostate cancer, substantiating the involvement of the EMT signaling events described in model systems. © 2012, American Society for Microbiology.
dc.format.extent
dc.format.extent Pages: (941-953)
dc.language English
dc.relation.ispartof Publication Name: Molecular and Cellular Biology; Publication Year: 2012; Volume: 32; no. 5; Pages: (941-953);
dc.relation.ispartofseries
dc.relation.uri
dc.source Scopus
dc.subject.other
dc.title Critical and reciprocal regulation of KLF4 and SLUG in transforming growth factor β-initiated prostate cancer epithelial-mesenchymal transition
dc.type Article
dc.contributor.affiliation Liu, Y.-N., Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
dc.contributor.affiliation Abou-Kheir, W., Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States, Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Yin, J.J., Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
dc.contributor.affiliation Fang, L., Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
dc.contributor.affiliation Hynes, P., Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
dc.contributor.affiliation Casey, O., Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
dc.contributor.affiliation Hu, D., Department of Cell Biology and Physiology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
dc.contributor.affiliation Wan, Y., Department of Cell Biology and Physiology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
dc.contributor.affiliation Seng, V., Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
dc.contributor.affiliation Sheppard-Tillman, H., Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
dc.contributor.affiliation Martin, P., Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States, Center for Advanced Preclinical Research, SAIC-NCI, Frederick, MD, United States
dc.contributor.affiliation Kelly, K., Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
dc.contributor.authorAddress Kelly, K.; Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States; email: kellyka@mail.nih.gov
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Anatomy, Cell Biology and Physiological Sciences;
dc.contributor.authorDepartment Anatomy, Cell Biology and Physiological Sciences
dc.contributor.authorDivision
dc.contributor.authorEmail
dc.contributor.authorFaculty Faculty of Medicine
dc.contributor.authorInitials
dc.contributor.authorOrcidID
dc.contributor.authorReprintAddress
dc.contributor.authorResearcherID
dc.contributor.authorUniversity American University of Beirut Medical Center
dc.description.cited
dc.description.citedCount 30
dc.description.citedTotWOSCount
dc.description.citedWOSCount
dc.format.extentCount 13
dc.identifier.articleNo
dc.identifier.coden MCEBD
dc.identifier.pubmedID 22203039
dc.identifier.scopusID 84863160718
dc.identifier.url
dc.publisher.address
dc.relation.ispartofConference
dc.relation.ispartofConferenceCode
dc.relation.ispartofConferenceDate
dc.relation.ispartofConferenceHosting
dc.relation.ispartofConferenceLoc
dc.relation.ispartofConferenceSponsor
dc.relation.ispartofConferenceTitle
dc.relation.ispartofFundingAgency
dc.relation.ispartOfISOAbbr
dc.relation.ispartOfIssue 5
dc.relation.ispartOfPart
dc.relation.ispartofPubTitle Molecular and Cellular Biology
dc.relation.ispartofPubTitleAbbr Mol. Cell. Biol.
dc.relation.ispartOfSpecialIssue
dc.relation.ispartOfSuppl
dc.relation.ispartOfVolume 32
dc.source.ID
dc.type.publication Journal
dc.subject.otherAuthKeyword
dc.subject.otherChemCAS uvomorulin, 112956-45-3
dc.subject.otherChemCAS Foxa1 protein, mouse
dc.subject.otherChemCAS GKLF protein
dc.subject.otherChemCAS Hepatocyte Nuclear Factor 3-alpha
dc.subject.otherChemCAS Kruppel-Like Transcription Factors
dc.subject.otherChemCAS Transcription Factors
dc.subject.otherChemCAS Transforming Growth Factor beta
dc.subject.otherChemCAS snail family transcription factors
dc.subject.otherIndex CD24 antigen
dc.subject.otherIndex CDH2 protein
dc.subject.otherIndex cell protein
dc.subject.otherIndex cytokeratin 18
dc.subject.otherIndex cytokeratin 8
dc.subject.otherIndex epithelial cell adhesion molecule
dc.subject.otherIndex hepatocyte nuclear factor 3alpha
dc.subject.otherIndex histone H3
dc.subject.otherIndex kruppel like factor 4
dc.subject.otherIndex messenger RNA
dc.subject.otherIndex polycomb group protein
dc.subject.otherIndex transcription factor Slug
dc.subject.otherIndex transcription factor Snail
dc.subject.otherIndex transforming growth factor beta
dc.subject.otherIndex unclassified drug
dc.subject.otherIndex uvomorulin
dc.subject.otherIndex vimentin
dc.subject.otherIndex ZEB1 protein
dc.subject.otherIndex ZEB2 protein
dc.subject.otherIndex animal cell
dc.subject.otherIndex animal experiment
dc.subject.otherIndex animal model
dc.subject.otherIndex animal tissue
dc.subject.otherIndex article
dc.subject.otherIndex binding site
dc.subject.otherIndex cancer growth
dc.subject.otherIndex cancer invasion
dc.subject.otherIndex controlled study
dc.subject.otherIndex enhancer region
dc.subject.otherIndex epithelial mesenchymal transition
dc.subject.otherIndex gene silencing
dc.subject.otherIndex genetic transcription
dc.subject.otherIndex human
dc.subject.otherIndex human cell
dc.subject.otherIndex male
dc.subject.otherIndex malignant transformation
dc.subject.otherIndex mouse
dc.subject.otherIndex nonhuman
dc.subject.otherIndex priority journal
dc.subject.otherIndex promoter region
dc.subject.otherIndex prostate adenocarcinoma
dc.subject.otherIndex prostate cancer
dc.subject.otherIndex protein binding
dc.subject.otherIndex protein degradation
dc.subject.otherIndex protein expression
dc.subject.otherIndex sarcoma
dc.subject.otherIndex Animals
dc.subject.otherIndex Cell Line, Tumor
dc.subject.otherIndex Clone Cells
dc.subject.otherIndex Epithelial-Mesenchymal Transition
dc.subject.otherIndex Gene Expression Regulation, Neoplastic
dc.subject.otherIndex Hepatocyte Nuclear Factor 3-alpha
dc.subject.otherIndex Humans
dc.subject.otherIndex Kruppel-Like Transcription Factors
dc.subject.otherIndex Male
dc.subject.otherIndex Mice
dc.subject.otherIndex Prostatic Neoplasms
dc.subject.otherIndex Signal Transduction
dc.subject.otherIndex Transcription Factors
dc.subject.otherIndex Transcription, Genetic
dc.subject.otherIndex Transforming Growth Factor beta
dc.subject.otherKeywordPlus
dc.subject.otherWOS


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