The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets
Mariano F. Zacarías Fluck, Toni Jauset, Sandra Martínez-Martín, Jastrinjan Kaur, Sílvia Casacuberta‐Serra, Daniel Massó-Vallés, Erika Serrano del Pozo, Génesis Martín-Fernández, Íñigo González-Larreategui, Sergio López‐Estévez, Lamorna Brown Swigart, Marie-Ève Beaulieu, Jonathan R. Whitfield, Babita Madan, David M. Virshup, Gérard I. Evan, Laura Soucek
Abstract
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.