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Mucoepidermoid carcinoma (MEC) progression is driven by an FGFR-p53 developmental signaling axis, which is shared between MEC tumors and fetal salivary glands. This axis implicates proliferative and developmental gene expression profiles in MEC progression. The study suggests a role for FGFR targeted therapies in treating high-grade MEC.

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What they did

System
MEC

What worked

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Abstract

Mucoepidermoid carcinoma (MEC) is the most frequently occurring salivary gland malignancy. Here, we investigated transcriptomic profiles of human fetal and adult salivary glands and MEC tumors to assess programs involved in MEC progression. Molecular and genetic analyses revealed that MEC tumors and fetal salivary glands share proliferative and developmental gene expression profiles that implicate an FGFR-p53 signaling axis in salivary MEC progression. Based on these findings, we developed a genetically engineered mouse model of advanced MEC via targeted expression of the CRTC1-MAML2 oncogene in salivary ductal cells. Specifically, CRTC1-MAML2 expression combined with p53 dysregulation in salivary ducts rewires FGF signaling to drive formation of tumors with histological and molecular features of high-grade MEC. The combined bioinformatics and mouse modeling of this study demonstrate that salivary MEC progression is underpinned by reactivation of developmental signaling programs and suggests a role for FGFR targeted therapies in the treatment of high-grade MEC.

Key findings

  • MEC tumors and fetal salivary glands share proliferative and developmental gene expression profiles
  • FGFR-p53 signaling axis is implicated in salivary MEC progression
  • CRTC1-MAML2 expression combined with p53 dysregulation drives formation of high-grade MEC tumors

Keywords

CancerFibroblast growth factor receptorCarcinogenesisSignal transductionCancer researchFibroblast growth factor

Identifiers

DOI
10.1038/s41388-025-03444-7
PubMed
40456865
Journal
Oncogene
Year
2025