Heterospecific developmental models highlight the role of FBXO32 in neural crest lineages and the significance of its variant in pediatric melanoma - Archive ouverte HAL Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2023

Heterospecific developmental models highlight the role of FBXO32 in neural crest lineages and the significance of its variant in pediatric melanoma

Résumé

Melanoma is a rare sporadic pediatric cancer caused by de novo genetic accidents. To analyze the involvement of FBXO32 of unknown biological significance, we set up original developmental in vivo, ex vivo, and in vitro models to unmask the biological role of FBXO32 in cephalic and trunk neural crest lineages. We show that FBXO32 silencing impairs melanocyte proliferation, differentiation, and vascularization. In rescue experiments, co-electroporation with the human wild-type gene compensates for the silencing of the endogenous gene and restores normal melanocyte phenotypes. By contrast, co-electroporation with the human variant, FBXO32G139S, alters melanocyte differentiation, pigment synthesis, triggers migration to the dermis, and favors angiotropism. Transcriptomic analysis reveals targets associated with melanocyte transformation, cytoskeleton remodeling, and focal adhesion. We show that FBXO32 orchestrates unexpected interactions with ASIP for melanogenesis and BAP1 for the post-translational ubiquitination system. We propose FBXO32 as a tumor suppressor gene capable of preventing the onset of pediatric melanoma.
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Dates et versions

hal-04030092 , version 1 (15-03-2023)

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Vargas Alexandra, Clémence Guillermain, Gorojankina Tatiana, Creuzet Sophie. Heterospecific developmental models highlight the role of FBXO32 in neural crest lineages and the significance of its variant in pediatric melanoma. 2023. ⟨hal-04030092⟩
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