Hippo 信号传导参与控制组织稳态和器官大小的细胞外信号的协调。 Yes 相关蛋白 1 (YAP1) 主要由 Hippo 信号传导通过转录因子与称为 TEAD 的 GATA 结构域的共激活来调节。然而，由于 YAP1 通过平坦界面与 TEAD4 紧密结合，因此很难开发 YAP1 的小分子正位抑制剂。先前的研究表明，氯丙嗪（CPZ）可以抑制YAP1的表达。通过MTT、集落形成、伤口愈合、Transwell迁移和Western blot实验来探讨CPZ如何通过FOXP3影响鼻咽癌（NPC）细胞。此外，免疫荧光和活细胞成像用于检测 CPZ 给药后 YAP1 的细胞内定位。通过HDOCK网站，我们预测了FOXP3和TEAD4之间的蛋白质结合区域。采用Western blot和co-IP实验验证FOXP3和YAP1之间的关系。使用UCSC Xena数据库、LinkedOmics数据库和KM绘图仪网站评估FOXP3在头颈鳞状细胞癌（HNSCC）中的预后价值。年龄、性别、病理肿瘤淋巴结转移 (pTMN) 分期、分级、吸烟状况和 FOXP3 表达均包含在总体生存列线图模型中。我们的研究结果表明，FOXP3 具有与 TEAD4 竞争性相互作用来抑制 YAP1 表达的能力。通过增加 FOXP3 表达，CPZ 诱导 YAP1 核输出和磷酸化，从而抑制 NPC 细胞增殖和迁移。总的来说，我们的研究结果表明，FOXP3 竞争性结合 TEAD4，调节 YAP1 在细胞核和细胞质中的定位，从而抑制 NPC 进展。因此，FOXP3 可能是 HNSCC 的预后指标。版权所有 © 2024 Elsevier Ltd。保留所有权利。

Hippo signalling is involved in the coordination of extracellular signals that control tissue homeostasis and organ size. Yes-associated protein 1 (YAP1) is regulated primarily by Hippo signalling through coactivation of transcription factors with GATA domains called TEADs. However, small-molecule orthosteric inhibitors of YAP1 are difficult to develop due to its tight binding to TEAD4 via a flat interface. Previous studies have shown that chlorpromazine (CPZ) can inhibit YAP1 expression. MTT, colony formation, wound healing, Transwell migration and Western blot assays were performed to explore how CPZ affects nasopharyngeal carcinoma (NPC) cells through FOXP3. In addition, immunofluorescence and live-cell imaging were used to detect YAP1 intracellular localization after CPZ administration. Through the HDOCK website, we predicted protein binding regions between FOXP3 and TEAD4. Western blot and co-IP experiments were used to verify the relationship between FOXP3 and YAP1. The UCSC Xena database, LinkedOmics database and KM plotter website were used to assess the prognostic value of FOXP3 in head and neck squamous cell carcinoma (HNSCC). Age, sex, pathological tumour-node-metastasis (pTMN) stage, grade, smoking status and FOXP3 expression were included in an overall survival nomogram model. Our findings revealed that FOXP3 has the ability to competitively interacts competitively with TEAD4 to inhibit YAP1 expression. By increasing FOXP3 expression, CPZ induces YAP1 nuclear export and phosphorylation, consequently suppressing NPC cell proliferation and migration. Collectively, our findings indicate that FOXP3 competitively binds TEAD4 to regulate YAP1 localization in the nucleus and cytoplasm to suppress NPC progression. Consequently, FOXP3 may be a prognostic indicator for HNSCC.Copyright © 2024 Elsevier Ltd. All rights reserved.