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. © 2021 Zacarías-Fluck et al.

Citation

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-Eve Beaulieu, Jonathan R Whitfield, Babita Madan, David M Virshup, Gerard I Evan, Laura Soucek. The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets. Life science alliance. 2021 May;4(5)

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PMID: 33653688

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