Orthodenticle homeobox (OTX1)据报道与许多癌症有关，但其在胆囊癌（GBC）中的表达水平和分子功能仍不清楚。我们发现，OTX1水平升高与人类胆囊癌的不良预后有关。人类胆囊癌细胞系的体外和体内研究表明，OTX1的过表达促进了细胞增殖，而下调则抑制了细胞增殖。此外，我们发现牛磺胆酸酯（TDCA）血清水平与OTX1表达密切相关。磷酸化抑制TDCA诱导的YAP1激活有助于OTX1的转录激活。机械上，我们确定了OTX1通过转录IFITM3的表达而激活AKT信号通路，从而促进GBC细胞的增殖。综上所述，我们的结果表明，TDCA-YAP1依赖性的OTX1表达通过AKT信号通路调控IFITM3，并影响胆囊癌的增殖。我们的实验也表明，OTX1是GBC的一种新的治疗靶点。©2023该作者（们），在Springer Nature有限公司的独家许可下。

Orthodenticle homeobox (OTX1) is reported to be involved in numerous cancers, but the expression level and molecular function of OTX1 in gallbladder cancer (GBC) remain unknown. Here, we found the elevated level of OTX1 associated with poor prognosis in human gallbladder cancer. In vitro and in vivo studies of human gallbladder cancer cell lines demonstrated that overexpression of OTX1 promoted cell proliferation, whereas the downregulation inhibited it. Additionally, we found a tight correlation between the serum level of taurodeoxycholic acid (TDCA) and OTX1 expression. TDCA-induced activation of YAP1 by phosphorylation inhibition contributed to the transcriptional activation of OTX1. Mechanistically, we identified that OTX1 activated AKT signaling pathway by transactivating the expression of IFITM3 and thus promoted the proliferation of GBC cells. Taken together, our results showed that TDCA-YAP1-dependent expression of OTX1 regulated IFITM3 and affected GBC proliferation via the AKT signaling pathway. Our experiments also suggested that OTX1 is a novel therapeutic target for GBC.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.