A new study has clarified the role of NOTCH1 in head and neck squamous cell carcinoma (HNSCC), showing that it functions as a tumor suppressor rather than an oncogene. Researchers found that activating NOTCH1 signaling in both mutated and wild-type cancer cells reduced tumor growth, lowered cancer stem cell activity, and triggered changes linked to cell differentiation and senescence. In lab and animal models, tumors with active NOTCH1 were less aggressive and had a much weaker ability to initiate new tumor growth.
Further molecular analysis showed that NOTCH1 suppresses cancer by driving tumor cells toward a more mature, differentiated state. This reduces cancer-promoting gene expression and weakens cell adhesion to surrounding tissue structures that support tumor expansion.
Patient data from The Cancer Genome Atlas confirmed these findings, identifying tumor groups with either active or inactive NOTCH1 signaling. Higher NOTCH1 activity was linked to better overall and progression-free survival, while low NOTCH1 combined with high NRF2 signaling was associated with the worst outcomes.