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

Abstract

HOX transcription factors are members of an evolutionarily conserved family of proteins required 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 as oncogenes or tumor suppressor genes are only partially understood. Since the MAPK/ERK signaling pathway is deregulated in most cancers, we aimed at apprehending if and how the Hox proteins interact with ERK oncogenicity. Using an in vivo neoplasia model in the chicken embryo consisting in the overactivation of the ERK1/2 kinases in the trunk neural tube, we analyzed the consequences of the HOXB8 gain of function at the morphological and transcriptional levels. We found that HOXB8 acts as a tumor suppressor, counteracting ERK-induced neoplasia. The HOXB8 tumor suppressor function relies on a large reversion of the oncogenic transcriptome induced by ERK. In addition to showing that the HOXB8 protein controls the transcriptional responsiveness to ERK oncogenic signaling, our study identified new downstream targets of ERK oncogenic activation in an in vivo context that could provide clues for therapeutic strategies.

Sustained experimental activation of FGF8/ERK in the developing chicken spinal cord models early events in ERK-mediated tumorigenesis

“…Cleaved caspase-3 (CASP3) immunofluorescence showed that MEK1ca expression also leads to an increase of cell death on the electroporated side ( Fig. 3 , see also quantification one day post-electroporation in [72] ). This increase of apoptosis is consistent with previous studies showing that ERK oncogenic activity, in addition to its well-described hyperproliferative effects, also promotes apoptosis, autophagy and senescence [9] .…”

The expression characteristics and clinical significance of ACP6, a potential target of nitidine chloride, in hepatocellular carcinoma

“…The serological testing and immunoblot assay by M Volkmann et al revealed humoral immune response to p53 exclusively in HCC patients and the presence of p53 antibodies in HCC patients was not dependent on alpha-fetoprotein level [ 35 ]. The mitogen-activated protein kinase (MAPK) signaling pathways played essential roles in diverse biological events including survival, dissemination, and resistance to drug therapy of human tumor cells [ 38 – 40 ]. Wang et al reported activation of MAPK signaling pathway during the promotion of HCC development stimulated by linc00601 upregulation [ 36 ].…”