Previously, we reported that stimulation of the NOTCH pathway in NOTCH1-wt HNSCC cell lines led to significant downregulation of two prominent proto-oncogenes, AXL and CTNNAL1 (α-catulin) [56], which have both been linked to aggressive biologic and clinical features in HNSCC and other tumor types [61,62,63]. The gene discussed is CTNNAL1; the disease is head and neck squamous cell carcinoma.