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. 2025 Aug;44(32):2876-2892.
doi: 10.1038/s41388-025-03444-7. Epub 2025 Jun 2.

An FGFR-p53 developmental signaling axis drives salivary cancer progression

Adele M Musicant #  1 , Julia M R Billington #  2   3 , Jeffrey S Damrauer  4 , Jennifer L Modliszewski  5 , Luane J B Landau  6 , Yi-Hsuan Tsai  5 , Jay H Mehta  3 , John Powers  3 , Renee Betancourt  7 , Radhika Sekhri  8 , Ricardo J Padilla  9 , Juan C Hernandez-Prera  10 , D Neil Hayes  8 , Trevor G Hackman  11 , Omer Gokcumen  6 , Sarah M Knox  12   13 , Antonio L Amelio  14   15
Affiliations

An FGFR-p53 developmental signaling axis drives salivary cancer progression

Adele M Musicant et al. Oncogene. 2025 Aug.

Erratum in

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.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics approval: Research involving human tissues was reviewed and approved by the Institutional Review Boards at The University of North Carolina at Chapel Hill (IRB protocols 15-1604 and 17-2947) and University of California—San Francisco (IRB protocol 10-00768) and informed consent was obtained from all participants. Research involving murine tissues was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of The University of North Carolina Chapel Hill (IACUC protocols 17-202 and 20-142), Moffitt Cancer Center and the University of South Florida (IACUC protocols 11291 M and 11379 R). All methods were performed in accordance with relevant guidelines and regulations.

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