Wang Weilong, Chang Tingmin, Wang Lingchao, Bin Mohamed Rafeezul, Binti Ahmad Nor Hazwani, Li Xiumin
Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province, PR China.
Department of Biomedical Science, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Pulau Pinang, Malaysia.
Ann Med. 2025 Dec;57(1):2536200. doi: 10.1080/07853890.2025.2536200. Epub 2025 Jul 22.
Yes-associated protein (YAP) is a core component of the Hippo pathway, which functions as an oncogene in various cancers. However, emerging evidence has shown that YAP can also act as a tumor suppressor. Therefore, understanding the function and molecular mechanism of YAP is crucial for developing YAP-targeted drugs in tumors.
A comprehensive literature review was conducted. The review mainly includes the post-translational modification, the regulatory mechanisms and function of YAP in esophageal squamous cell carcinoma (ESCC).
YAP undergoes various post-translational modifications (PTMs), including phosphorylation, ubiquitination, acetylation and others, which critically regulate its protein stability and transcriptional activity in multiple tumors, particularly ESCC. YAP is highly expressed in ESCC tissues, with its aberrant activation closely correlated with poor prognosis in patients. Additionally, YAP is involved in the progression of ESCC, including tumor migration, invasion, proliferation, cell stemness, apoptosis, therapeutic resistance, and immunity. In ESCC, YAP has been confirmed to be regulated by multiple upstream regulators, such as E3 ubiquitin ligases and kinases, thereby influencing the ESCC progression. However, there are still few drugs available clinically for YAP-targeted therapy, which requires further research. In this review, we systematically synthesize the biological roles and regulatory mechanisms of YAP in ESCC and outline potential research directions for YAP-targeted therapies, aiming to provide novel insights for precision medicine in ESCC.
YAP is closely correlated to ESCC progression, and it could be a promising target for ESCC treatment.
Yes相关蛋白（YAP）是Hippo信号通路的核心组成部分，在多种癌症中发挥癌基因作用。然而，新出现的证据表明YAP也可作为肿瘤抑制因子。因此，了解YAP的功能和分子机制对于开发针对肿瘤的YAP靶向药物至关重要。
进行了全面的文献综述。该综述主要包括YAP在食管鳞状细胞癌（ESCC）中的翻译后修饰、调控机制及功能。
YAP经历多种翻译后修饰（PTM），包括磷酸化、泛素化、乙酰化等，这些修饰在多种肿瘤尤其是ESCC中严格调控其蛋白质稳定性和转录活性。YAP在ESCC组织中高表达，其异常激活与患者预后不良密切相关。此外，YAP参与ESCC的进展，包括肿瘤迁移、侵袭、增殖、细胞干性、凋亡、治疗抗性及免疫。在ESCC中，YAP已被证实受多种上游调节因子调控，如E3泛素连接酶和激酶，从而影响ESCC进展。然而，临床上仍缺乏针对YAP靶向治疗的药物，这需要进一步研究。在本综述中，我们系统总结了YAP在ESCC中的生物学作用和调控机制，并概述了YAP靶向治疗的潜在研究方向，旨在为ESCC的精准医学提供新见解。
YAP与ESCC进展密切相关，可能是ESCC治疗的一个有前景的靶点。
