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

   

Authors:	Wang, G.; Lunardi, A.; Zhang, J.; Chen, Z.; Ala, U.; Webster, K. A.; Tay, Y.; Gonzalez-Billalabeitia, E.; Egia, A.; Shaffer, D. R.; Carver, B.; Liu, X. S.; Taulli, R.; Kuo, W. P.; Nardella, C.; Signoretti, S.; Cordon-Cardo, C.; Gerald, W. L.; Pandolfi, P. P.
Article Title:	Zbtb7a suppresses prostate cancer through repression of a Sox9-dependent pathway for cellular senescence bypass and tumor invasion
Abstract:	Zbtb7a 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.
Keywords:	signal transduction; controlled study; dna-binding proteins; nonhuman; animal cell; mouse; animals; mice; animal tissue; proto oncogene; microrna; models, biological; animal experiment; animal model; down-regulation; cell line, tumor; mice, inbred c57bl; carcinogenesis; mice, transgenic; transcription factors; cell transformation, neoplastic; prostate cancer; prostatic neoplasms; cancer inhibition; gene expression regulation, neoplastic; messenger rna; nucleotide sequence; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; pten phosphohydrolase; tumor cell; down regulation; neoplasm invasiveness; senescence; tumor gene; cell aging; cell invasion; genes, tumor suppressor; transcription factor sox9; sox9 transcription factor; tumor invasion; zbtb7a gene
Journal Title:	Nature Genetics
Volume:	45
Issue:	7
ISSN:	1061-4036
Publisher:	Nature Publishing Group
Date Published:	2013-06-01
Start Page:	739
End Page:	746
Language:	English
DOI:	10.1038/ng.2654
PROVIDER:	scopus
PUBMED:	23727861
PMCID:	PMC4036521
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84879645484&partnerID=40&md5=dcae7f2a6d95a9a29a4cf601665683b3
Notes:	--- - Cited By (since 1996):2 - "Export Date: 1 August 2013" - "CODEN: NGENE" - "Molecular Sequence Numbers: GENBANK: GSE46473;" - "Source: Scopus"

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