The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets.
The huge cadre of genes regulated by Myc has obstructed the identification of critical effectors that are essential for Myc-driven tumorigenesis. Here, we describe how only the lack of the receptor Fzd9, previously identified as a Myc transcriptional target, impairs sustained tumor expansion and β-cell dedifferentiation in a mouse model of Myc-driven insulinoma, allows pancreatic islets to maintain their physiological structure and affects Myc-related global gene expression. Importantly, Wnt signaling inhibition in Fzd9-competent mice largely recapitulates the suppression of proliferation caused by Fzd9 deficiency upon Myc activation. Together, our results indicate that the Wnt signaling receptor Fzd9 is essential for Myc-induced tumorigenesis in pancreatic islets.
Zacarías-Fluck, MF; Jauset, T; Martínez-Martín, S; Kaur, J; Casacuberta-Serra, S; Massó-Vallés, D; Serrano Del Pozo, E; Martín-Fernández, G; González-Larreategui, Í; López-Estévez, S; Brown-Swigart, L; Beaulieu, M-E; Whitfield, JR; Madan, B; Virshup, DM; Evan, GI; Soucek, L
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