Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/6247
Share/Export:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Title

FUS-DDIT3 prevents the development of adipocytic precursors in liposarcoma by repressing PPARγ and C/EBPα and activating eIF4E

AuthorsPérez-Mancera, P. A.; Bermejo-Rodríguez, C.; Sánchez-Martín, M.; Abollo-Jiménez, Fernando CSIC; Pintado, Belén; Sánchez García, Isidro CSIC ORCID
KeywordsCancer stem cells
Liposarcoma
Issue Date2008
PublisherPublic Library of Science
CitationPLoS ONE 3(7): e2569 (2008)
AbstractFUS-DDIT3 is a chimeric protein generated by the most common chromosomal translocation t(12;16)(q13;p11) linked to liposarcomas, which are characterized by the accumulation of early adipocytic precursors. Current studies indicate that FUS-DDIT3- liposarcoma develops from uncommitted progenitors. However, the precise mechanism whereby FUS-DDIT3 contributes to the differentiation arrest remains to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Here we have characterized the adipocyte regulatory protein network in liposarcomas of FUS-DITT3 transgenic mice and showed that PPARgamma2 and C/EBPalpha expression was altered. Consistent with in vivo data, FUS-DDIT3 MEFs and human liposarcoma cell lines showed a similar downregulation of both PPARgamma2 and C/EBPalpha expression. Complementation studies with PPARgamma but not C/EBPalpha rescued the differentiation block in committed adipocytic precursors expressing FUS-DDIT3. Our results further show that FUS-DDIT3 interferes with the control of initiation of translation by upregulation of the eukaryotic translation initiation factors eIF2 and eIF4E both in FUS-DDIT3 mice and human liposarcomas cell lines, explaining the shift towards the truncated p30 isoform of C/EBPalpha in liposarcomas. Suppression of the FUS-DDIT3 transgene did rescue this adipocyte differentiation block. Moreover, eIF4E was also strongly upregulated in normal adipose tissue of FUS-DDIT3 transgenic mice, suggesting that overexpression of eIF4E may be a primary event in the initiation of liposarcomas. Reporter assays showed FUS-DDIT3 is involved in the upregulation of eIF4E in liposarcomas and that both domains of the fusion protein are required for affecting eIF4E expression. CONCLUSIONS/SIGNIFICANCE: Taken together, this study provides evidence of the molecular mechanisms involve in the disruption of normal adipocyte differentiation program in liposarcoma harbouring the chimeric gene FUS-DDIT3.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pone.0002569
URIhttp://hdl.handle.net/10261/6247
DOI10.1371/journal.pone.0002569
ISSN1932-6203
Appears in Collections:(IBMCC) Artículos
(CNB) Artículos

Files in This Item:
File Description SizeFormat
13a-journal.pone.0002569.pdf2,77 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work

PubMed Central
Citations

19
checked on May 17, 2022

SCOPUSTM   
Citations

38
checked on May 25, 2022

WEB OF SCIENCETM
Citations

35
checked on May 26, 2022

Page view(s)

405
checked on May 26, 2022

Download(s)

231
checked on May 26, 2022

Google ScholarTM

Check

Altmetric

Dimensions


Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.