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Article: Zbtb7a suppresses prostate cancer through repression of a Sox9-dependent pathway for cellular senescence bypass and tumor invasion

TitleZbtb7a suppresses prostate cancer through repression of a Sox9-dependent pathway for cellular senescence bypass and tumor invasion
Authors
KeywordsAnimals
Cell Aging/*genetics
Cell Line, Tumor
Cell Transformation, Neoplastic/genetics
DNA-Binding Proteins/genetics/metabolism/*physiology
Down-Regulation/genetics
Female
Gene Expression Regulation, Neoplastic/physiology
*Genes, Tumor Suppressor/physiology
Humans
Mice
Mice, Inbred C57BL
Issue Date2013
PublisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
Citation
Nature Genetics, 2013, v. 45 n. 7, p. 739-746 How to Cite?
AbstractZbtb7a has previously been described as a powerful proto-oncogene. Here we unexpectedly demonstrate that Zbtb7a has a critical oncosuppressive role in the prostate. Prostate-specific inactivation of Zbtb7a leads to a marked acceleration of Pten loss-driven prostate tumorigenesis through bypass of Pten loss-induced cellular senescence (PICS). We show that ZBTB7A physically interacts with SOX9 and functionally antagonizes its transcriptional activity on key target genes such as MIA, which is involved in tumor cell invasion, and H19, a long noncoding RNA precursor for an RB-targeting microRNA. Inactivation of Zbtb7a in vivo leads to Rb downregulation, PICS bypass and invasive prostate cancer. Notably, we found that ZBTB7A is genetically lost, as well as downregulated at both the mRNA and protein levels, in a subset of human advanced prostate cancers. Thus, we identify ZBTB7A as a context-dependent cancer gene that can act as an oncogene in some contexts but also has oncosuppressive-like activity in PTEN-null tumors. © 2013 Nature America, Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/219915
ISSN
2015 Impact Factor: 31.616
2015 SCImago Journal Rankings: 23.762
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, G-
dc.contributor.authorLunardi, A-
dc.contributor.authorZhang, J-
dc.contributor.authorChen, Z-
dc.contributor.authorAla, U-
dc.contributor.authorWebster, KA-
dc.contributor.authorTay, Y-
dc.contributor.authorGonzalez-Billalabeitia, E-
dc.contributor.authorEgia, A-
dc.contributor.authorShaffer, DR-
dc.contributor.authorCarver, B-
dc.contributor.authorLiu, XS-
dc.contributor.authorTaulli, R-
dc.contributor.authorKuo, WP-
dc.contributor.authorNardella, C-
dc.contributor.authorSignoretti, S-
dc.contributor.authorCordon-Cardo, C-
dc.contributor.authorGerald, WL-
dc.contributor.authorPandolfi, PP-
dc.date.accessioned2015-10-02T06:37:14Z-
dc.date.available2015-10-02T06:37:14Z-
dc.date.issued2013-
dc.identifier.citationNature Genetics, 2013, v. 45 n. 7, p. 739-746-
dc.identifier.issn1061-4036-
dc.identifier.urihttp://hdl.handle.net/10722/219915-
dc.description.abstractZbtb7a has previously been described as a powerful proto-oncogene. Here we unexpectedly demonstrate that Zbtb7a has a critical oncosuppressive role in the prostate. Prostate-specific inactivation of Zbtb7a leads to a marked acceleration of Pten loss-driven prostate tumorigenesis through bypass of Pten loss-induced cellular senescence (PICS). We show that ZBTB7A physically interacts with SOX9 and functionally antagonizes its transcriptional activity on key target genes such as MIA, which is involved in tumor cell invasion, and H19, a long noncoding RNA precursor for an RB-targeting microRNA. Inactivation of Zbtb7a in vivo leads to Rb downregulation, PICS bypass and invasive prostate cancer. Notably, we found that ZBTB7A is genetically lost, as well as downregulated at both the mRNA and protein levels, in a subset of human advanced prostate cancers. Thus, we identify ZBTB7A as a context-dependent cancer gene that can act as an oncogene in some contexts but also has oncosuppressive-like activity in PTEN-null tumors. © 2013 Nature America, Inc. All rights reserved.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com-
dc.relation.ispartofNature Genetics-
dc.subjectAnimals-
dc.subjectCell Aging/*genetics-
dc.subjectCell Line, Tumor-
dc.subjectCell Transformation, Neoplastic/genetics-
dc.subjectDNA-Binding Proteins/genetics/metabolism/*physiology-
dc.subjectDown-Regulation/genetics-
dc.subjectFemale-
dc.subjectGene Expression Regulation, Neoplastic/physiology-
dc.subject*Genes, Tumor Suppressor/physiology-
dc.subjectHumans-
dc.subjectMice-
dc.subjectMice, Inbred C57BL-
dc.titleZbtb7a suppresses prostate cancer through repression of a Sox9-dependent pathway for cellular senescence bypass and tumor invasion-
dc.typeArticle-
dc.identifier.emailZhang, J: jzhang1@hku.hk-
dc.identifier.authorityZhang, J=rp01713-
dc.identifier.doi10.1038/ng.2654-
dc.identifier.pmid23727861-
dc.identifier.pmcidPMC4036521-
dc.identifier.scopuseid_2-s2.0-84879645484-
dc.identifier.volume45-
dc.identifier.issue7-
dc.identifier.spage739-
dc.identifier.epage746-
dc.identifier.isiWOS:000321005200008-
dc.publisher.placeUnited States-

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