LAUSR

Oral squamous cell carcinoma (OSCC) represents a clinical challenge due to the lack of effective therapy to improve prognosis. Hippo/Yes‐associated protein (YAP) signaling has emerged as a promising therapeutic target for squamous cell carcinoma treatment. In this study, we investigated the antitumor activity and underlying mechanisms of {[N‐(4‐(5‐(3‐(3‐(4‐acetamido‐3‐(trifluoromethyl)phenyl)ureido)phenyl)‐1,2,4‐oxadiazol‐3‐yl)‐3‐chlorophenyl)‐nicotinamide]} (ATN), a novel YAP inhibitor, in OSCC cells. ATN exhibited differential antiproliferative efficacy against OSCC cells (IC50 as low as 0.29 μM) versus nontumorigenic human fibroblast cells (IC50 = 1.9 μM). Moreover, ATN effectively suppressed the expression of YAP and YAP‐related or downstream targets, including Akt, p‐AMPK, c‐Myc, and cyclin D1, which paralleled the antiproliferative efficacy of ATN. Supporting the roles of YAP in regulating cancer cell survival and migration, ATN not only induced caspase‐dependent apoptosis, but also suppressed migration activity in OSCC. Mechanistically, the antitumor activity of ATN in OSCC was attributed, in part, to its ability to regulate Mcl‐1 expression. Together, these findings suggest a translational potential of YAP inhibitors, represented by ATN as anticancer therapy for OSCC.