Autoregulatory loop of nuclear corepressor 1 expression controls invasion, tumor growth, and metastasis
Author
Martínez-Iglesias, Olaia A.; Alonso-Merino, Elvira; Gómez-Rey, Sara; Velasco-Martín, Juan Pedro; Martín Orozco, Rosa; Luengo, Enrique; García Martín, Rosa; Ibáñez de Cáceres, Inmaculada; Fernández, Agustín F.; Fraga, María F.; González-Peramato Gutiérrez, María del Pilar; Varona, Constantino; Palacios, José; Regadera, Javier; Aranda, AnaEntity
UAM. Departamento de Anatomía Patológica; UAM. Departamento de Anatomía, Histología y Neurociencia; Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)Publisher
National Academy of SciencesDate
2016-01-04Citation
10.1073/pnas.1520469113
Proceedings of the National Academy of Sciences of the United States of America 113.3 (2016): E328
ISSN
1091-6490DOI
10.1073/pnas.1520469113Funded by
This work was supported by Grants BFU2011-28058 and BFU2014-53610-P from Ministerio de Economía y Competitividad; Grant S2011/BMD-2328 from the Comunidad de Madrid; Grant RD12/0036/0030 from the Instituto de Salud Carlos III (to A.A.); Grants PI080971 and RD12 0036/0064 from the Instituto de Salud Carlos III (to J.P.); and Grant PI12/00386 from the Instituto de Salud Carlos III (to I.I.d.C.). O.A.M.-I. is supported by an Asociación Española Contra el Cáncer contractProject
Gobierno de España. BFU2011-28058; Gobierno de España. BFU2014-53610-P; Comunidad de Madrid. S2011/BMD-2328/TIRONETEditor's Version
http://dx.doi.org/10.1073/pnas.1520469113Subjects
Nuclear corepressor 1; Thyroid hormone receptor; Tumor growth; Metastasis; Transcription; MedicinaAbstract
Nuclear corepressor 1 (NCoR) associates with nuclear receptors and
other transcription factors leading to transcriptional repression.
We show here that NCoR depletion enhances cancer cell invasion
and increases tumor growth and metastatic potential in nude
mice. These changes are related to repressed transcription of genes
associated with increased metastasis and poor prognosis in patients.
Strikingly, transient NCoR silencing leads to heterochromatinization
and stable silencing of the NCoR gene, suggesting that NCoR loss can
be propagated, contributing to tumor progression even in the absence
of NCoR gene mutations. Down-regulation of the thyroid hormone
receptor β1 (TRβ) appears to be associated with cancer onset
and progression. We found that expression of TRβ increases NCoR
levels and that this induction is essential in mediating inhibition of
tumor growth and metastasis by this receptor. Moreover, NCoR is
down-regulated in human hepatocarcinomas and in the more aggressive
breast cancer tumors, and its expression correlates positively
with that of TRβ. These data provide a molecular basis for the anticancer
actions of this corepressor and identify NCoR as a potential
molecular target for development of novel cancer therapies
Files in this item
Google Scholar:Martínez-Iglesias, Olaia A.
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Alonso-Merino, Elvira
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Gómez-Rey, Sara
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Velasco-Martín, Juan Pedro
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Martín Orozco, Rosa
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Luengo, Enrique
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García Martín, Rosa
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Ibáñez de Cáceres, Inmaculada
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Fernández, Agustín F.
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Fraga, María F.
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González-Peramato Gutiérrez, María del Pilar
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Varona, Constantino
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Palacios, José
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Regadera, Javier
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Aranda, Ana
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