Mouse Models of Cancer Therapy Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
Peptomyc SL, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
Life Sci Alliance. 2021 Mar 2;4(5). doi: 10.26508/lsa.201900490. Print 2021 May.
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.
Myc 调控的庞大基因库阻碍了关键效应因子的鉴定，而这些效应因子对于 Myc 驱动的肿瘤发生是必不可少的。在这里，我们描述了仅缺乏受体 Fzd9（先前被鉴定为 Myc 转录靶标）如何在 Myc 驱动的胰岛素瘤的小鼠模型中损害持续的肿瘤扩张和β细胞去分化，使胰岛能够维持其生理结构并影响 Myc 相关的全局基因表达。重要的是，在 Fzd9 功能正常的小鼠中抑制 Wnt 信号传导在很大程度上再现了 Myc 激活时 Fzd9 缺失引起的增殖抑制。总之，我们的结果表明，Wnt 信号受体 Fzd9 对于胰腺胰岛中的 Myc 诱导的肿瘤发生是必需的。
