The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets

Mariano F. Zacarías-Fluck, Toni Jauset González, 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

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

Zacarías-Fluck, et al identify and validate the Wnt receptor Fzd9 as a key effector of Myc-Wnt signaling cross-talk in a mouse model of Myc-driven pancreatic insulinomas. 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.
Original languageEnglish
JournalLife Science Alliance
Volume4
DOIs
Publication statusPublished - 2021

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