JCI insight · 2026
NOTCH1 acts as a tumor suppressor that induces early differentiation in head and neck cancer.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Huang Chenfei, Moorthy Shhyam, Li Qiuli, Ahmed Kazi M, Saab Kalil, Deng Defeng, Wang Jiping, Rao Xiayu, Zhang Jiexin, Xi Yuanxin, Wang Jing, Liu Zhiyi, Tanaka Noriaki, Wheeler David A, Shinbrot Eve, Saade Rami, Pickering Curtis R, Xie Tong-Xin, El-Naggar Adel K, Osman Abdullah A, Rai Kunal, Zweidler-McKay Patrick A, Heymach John V, Byers Lauren A, Johnson Faye M, Sandulache Vlad C, Myers Jeffrey N, Yadollahi Pedram, Frederick Mitchell J
Аннотация
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.