SQLE is crucial for HNSCC initiation and progression, and pharmacological inhibition of SQLE sensitizes cancer cells to cisplatin in vivo. a) Schematic diagram illustrating the determination of Sqle conditional KO effects in oral epithelial cells on HNSCC initiation. b,c) Representative images of tongue lesions and tumor lesion area in Sqle
CTRL and Sqle
cKO mice (n = 12). d) Representative histological images of tongue lesions in Sqle
CTRL and Sqle
cKO mice. e) Metastatic lymph nodes in Sqle
CTRL and Sqle
cKO groups (n = 12). f) Schematic diagram evaluating the effects of Sqle conditional KO on HNSCC development. g,h) Representative gross and histological images of tongue lesions in Sqle
CTRL and Sqle
cKO mice. i,j) Tumor lesion area and metastatic lymph nodes in Sqle
CTRL and Sqle
cKO groups (n = 12). k) Schematic diagram evaluating the combined use of terbinafine and cisplatin in reducing tumor growth in orthotopic mouse model. l) Representative images of tongue lesions from mice with indicated treatments. m,n) Tumor lesion area and metastatic lymph nodes in mice with indicated treatments (n = 12). o–q) Effects of terbinafine and cisplatin on suppressing tumor growth in the PDX model (n = 8). r) Western blot analyses of PCNA, CD44, SOX2, and KIF4 expression in xenograft tumor tissues subjected to indicated treatments. s) Proposed model depicting the regulation of c‐Myc by SQLE through lipid raft‐localized Akt. Scale bar: 200 µm. Data were presented as mean ± SD. ns (not significant), *p < 0.05, **p < 0.01, ***p < 0.001 for Student's t‐test and one‐way ANOVA test.