Four lines of experimental evidence to support a putative oncogenic function for NOTCH1 have been pervasive in this body of literature: (1) manipulation of NOTCH1 signaling in HNSCC cell lines alters tumor spheroid growth in vitro; (2) knockdown of total NOTCH1 expression with short hairpin RNA (shRNA) leads to reduced growth in vitro; (3) NOTCH1 expression and activation correlates with expression of cancer stem cell markers in vitro; (4) NOTCH1 activation can occur in primary HNSCC tumor samples and in some cases correlates with aggressive disease. This evidence concerns the gene NOTCH1 and cancer.