SPHK2 and cancer: Previous studies fromour group and others have shown that SK2 overexpression modulatesthe DNA damage response and enhancesthe stemness program. To explore howSK2 activation increases cancer stemness in HNSCC cells and mediatesresistance to DNA damage, we used orosphere cultures derived fromnontumor keratinocytes NOK-Ø/NOK-SK2 and HN13-Ø/HN13-shSK2cell lines, with or without UV irradiation (Figure S1A,B).