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http://purl.uniprot.org/citations/25157139http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25157139http://www.w3.org/2000/01/rdf-schema#comment"Pre-B-cell leukemia homeobox (Pbx)-regulating protein-1 (Prep1) is a ubiquitous homeoprotein involved in early development, genomic stability, insulin sensitivity, and hematopoiesis. Previously we have shown that Prep1 is a haploinsufficient tumor suppressor that inhibits neoplastic transformation by competing with myeloid ecotropic integration site 1 for binding to the common heterodimeric partner Pbx1. Epithelial-mesenchymal transition (EMT) is controlled by complex networks of proinvasive transcription factors responsive to paracrine factors such as TGF-β. Here we show that, in addition to inhibiting primary tumor growth, PREP1 is a novel EMT inducer and prometastatic transcription factor. In human non-small cell lung cancer (NSCLC) cells, PREP1 overexpression is sufficient to trigger EMT, whereas PREP1 down-regulation inhibits the induction of EMT in response to TGF-β. PREP1 modulates the cellular sensitivity to TGF-β by inducing the small mothers against decapentaplegic homolog 3 (SMAD3) nuclear translocation through mechanisms dependent, at least in part, on PREP1-mediated transactivation of a regulatory element in the SMAD3 first intron. Along with the stabilization and accumulation of PBX1, PREP1 induces the expression of multiple activator protein 1 components including the proinvasive Fos-related antigen 1 (FRA-1) oncoprotein. Both FRA-1 and PBX1 are required for the mesenchymal changes triggered by PREP1 in lung tumor cells. Finally, we show that the PREP1-induced mesenchymal transformation correlates with significantly increased lung colonization by cells overexpressing PREP1. Accordingly, we have detected PREP1 accumulation in a large number of human brain metastases of various solid tumors, including NSCLC. These findings point to a novel role of the PREP1 homeoprotein in the control of the TGF-β pathway, EMT, and metastasis in NSCLC."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.org/dc/terms/identifier"doi:10.1073/pnas.1407074111"xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Blasi F."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Di Fiore P.P."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Bianchi F."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Fernandez S."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Longobardi E."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Schulte D."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Mittelbronn M."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Verde P."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Harter P.N."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Iavarone F."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Pisati F."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Incoronato M."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Spaggiari L."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Talotta F."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Dardaei L."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Risolino M."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/author"Mandia N."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/name"Proc Natl Acad Sci U S A"xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/pages"E3775-84"xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/title"Transcription factor PREP1 induces EMT and metastasis by controlling the TGF-beta-SMAD3 pathway in non-small cell lung adenocarcinoma."xsd:string
http://purl.uniprot.org/citations/25157139http://purl.uniprot.org/core/volume"111"xsd:string
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