Language
English
Publication Date
6-8-2026
Journal
JCI Insight
DOI
10.1172/jci.insight.202414
PMID
41989846
PMCID
PMC13313506
PubMedCentral® Posted Date
4-16-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Inactivating NOTCH1 mutations in head and neck squamous cell carcinoma (HNSCC) were described over a decade ago, suggesting a tumor suppressor function - unlike its oncogenic role in other tumors. Today, much debate persists regarding a putative oncogenic role in HNSCC as well, with reports that NOTCH1 signaling drives tumor growth and a cancer stem cell (CSC) phenotype. In this work, comprehensive experiments unequivocally demonstrate that NOTCH1 is a tumor suppressor in HNSCC regardless of mutation or activation status and that it reduces CSC frequency. We developed a signature of NOTCH1 activation showing the pathway is associated with very early differentiation, an altered tumor microenvironment, and better prognosis. Clarifying whether NOTCH1 occasionally functions as an oncogenic driver in HNSCC is crucial to prognosis and personalized therapy. The results presented unify the field, reconcile conflicting data, and provide critical insights into the biological and clinical significance of NOTCH1, with broader implications in other squamous carcinomas with NOTCH1 mutations.
Keywords
Receptor, Notch1, Humans, Signal Transduction, Head and Neck Neoplasms, Cell Differentiation, Neoplastic Stem Cells, Squamous Cell Carcinoma of Head and Neck, Tumor Microenvironment, Cell Line, Tumor, Genes, Tumor Suppressor, Male, Animals, Mice, Cell biology, Oncology, Head and neck cancer, Stem Cells, Tumor suppressors
Published Open-Access
yes
Recommended Citation
Huang, Chenfei; Moorthy, Shhyam; Li, Qiuli; et al., "NOTCH1 Acts as a Tumor Suppressor That Induces Early Differentiation in Head and Neck Cancer" (2026). Faculty, Staff and Students Publications. 7444.
https://digitalcommons.library.tmc.edu/baylor_docs/7444