MYCN repression of Lifeguard/FAIM2 enhances neuroblastoma aggressiveness
Planells-Ferrer, L. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Urresti, J. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Soriano, Aroa (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Reix, Stéphanie (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Murphy, D. M. (Royal College of Surgeons and National Children's Research Centre Our Lady's Children's Hospital)
Ferreres Piñas, Joan Carles (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Borràs i Serres, Francesc Enric (Hospital Universitari Vall d'Hebron)
Gallego, Soledad (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Stallings, R. L. (Royal College of Surgeons and National Children's Research Centre Our Lady's Children's Hospital)
Moubarak, Rana S. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Segura, M. F. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Comella i Carnicé, Joan Xavier 1963- (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Fecha:	2014
Resumen:	Neuroblastoma (NBL) is the most common solid tumor in infants and accounts for 15% of all pediatric cancer deaths. Several risk factors predict NBL outcome: age at the time of diagnosis, stage, chromosome alterations and MYCN (V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma-Derived Homolog) amplification, which characterizes the subset of the most aggressive NBLs with an overall survival below 30%. MYCN-amplified tumors develop exceptional chemoresistance and metastatic capacity. These properties have been linked to defects in the apoptotic machinery, either by silencing components of the extrinsic apoptotic pathway (e. g. caspase-8) or by overexpression of antiapoptotic regulators (e. g. Bcl-2, Mcl-1 or FLIP). Very little is known on the implication of death receptors and their antagonists in NBL. In this work, the expression levels of several death receptor antagonists were analyzed in multiple human NBL data sets. We report that Lifeguard (LFG/FAIM2 (Fas apoptosis inhibitory molecule 2)/NMP35) is downregulated in the most aggressive and undifferentiated tumors. Intringuingly, although LFG has been initially characterized as an antiapoptotic protein, we have found a new association with NBL differentiation. Moreover, LFG repression resulted in reduced cell adhesion, increased sphere growth and enhanced migration, thus conferring a higher metastatic capacity to NBL cells. Furthermore, LFG expression was found to be directly repressed by MYCN at the transcriptional level. Our data, which support a new functional role for a hitherto undiscovered MYCN target, provide a new link between MYCN overexpression and increased NBL metastatic properties.
Ayudas:	Ministerio de Ciencia e Innovación SAF2010-19953 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-346
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Apoptosis Regulatory Proteins ; Cell Adhesion ; Cell Differentiation
Publicado en:	Cell death and disease, Vol. 5 (09 2014) , p. e1401, ISSN 2041-4889

DOI: 10.1038/cddis.2014.356
PMID: 25188511

12 p, 1.8 MB

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