HOXB8 Counteracts MAPK/ERK Oncogenic Signaling in a Chicken Embryo Model of Neoplasia

Archive ouverte

Wilmerding, Axelle | Bouteille, Lauran | Rinaldi, Lucrezia | Caruso, Nathalie | Graba, Yacine | Delfini, Marie-Claire

Edité par CCSD ; MDPI -

International audience. HOX transcription factors are members of an evolutionarily conserved family of proteinsrequired for the establishment of the anteroposterior body axis during bilaterian development.Although they are often deregulated in cancers, the molecular mechanisms by which they act asoncogenes or tumor suppressor genes are only partially understood. Since the MAPK/ERK signalingpathway is deregulated in most cancers, we aimed at apprehending if and how the Hox proteinsinteract with ERK oncogenicity. Using an in vivo neoplasia model in the chicken embryo consistingin the overactivation of the ERK1/2 kinases in the trunk neural tube, we analyzed the consequencesof the HOXB8 gain of function at the morphological and transcriptional levels. We found that HOXB8acts as a tumor suppressor, counteracting ERK-induced neoplasia. The HOXB8 tumor suppressorfunction relies on a large reversion of the oncogenic transcriptome induced by ERK. In additionto showing that the HOXB8 protein controls the transcriptional responsiveness to ERK oncogenicsignaling, our study identified new downstream targets of ERK oncogenic activation in an in vivocontext that could provide clues for therapeutic strategies.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion