Ou Chunlin, Sun Zhenqiang, Li Shen, Li Guiyuan, Li Xiayu, Ma Jian
Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.
Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.
Oncotarget. 2017 Aug 11;8(43):75727-75741. doi: 10.18632/oncotarget.20155. eCollection 2017 Sep 26.
Yes-associated protein (YAP) is a downstream effector molecule of a newly emerging tumour suppressor pathway called the Hippo pathway. YAP is a transcriptional co-activator and mis-expressed in various cancers, including colorectal cancer (CRC). Accumulating studies show that the high expression of nuclear YAP is linked with tumour progression and decreased survival. Nuclear YAP can interact with other transcription factors to promote cancer cell proliferation, apoptosis, metastasis and maintenance of stemness. Therefore, YAP has the potential to be a tumour biomarker or therapeutic target for CRC. However, recently, a number of studies have supported a contradictory role for YAP as a tumour suppressor, demonstrating inhibition of the tumorigenesis of CRC, involvement in promoting cell apoptosis, and inhibiting the maintenance of intestinal stem cells and inflammatory activity. In these studies, high expression of YAP was highly correlated with worse survival in CRC. In this review, we will comprehensively summarize and analyse these paradoxical reports, and discuss both the oncogenic and tumour suppressor functions of YAP in the differential status of CRC progression. Further investigation into the mechanisms responsible for the dual function of YAP will be of great value in the prevention, early diagnosis, and therapy of CRC.
Yes相关蛋白（YAP）是一种新出现的名为Hippo通路的肿瘤抑制途径的下游效应分子。YAP是一种转录共激活因子，在包括结直肠癌（CRC）在内的多种癌症中表达异常。越来越多的研究表明，核YAP的高表达与肿瘤进展和生存率降低有关。核YAP可与其他转录因子相互作用，促进癌细胞增殖、凋亡、转移和干性维持。因此，YAP有可能成为CRC的肿瘤生物标志物或治疗靶点。然而，最近，一些研究支持YAP作为肿瘤抑制因子的矛盾作用，证明其抑制CRC的肿瘤发生、参与促进细胞凋亡以及抑制肠干细胞的维持和炎症活性。在这些研究中，YAP的高表达与CRC患者较差的生存率高度相关。在本综述中，我们将全面总结和分析这些矛盾的报道，并讨论YAP在CRC进展不同阶段的致癌和肿瘤抑制功能。进一步研究YAP双重功能的机制对于CRC的预防、早期诊断和治疗具有重要价值。
