Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Oncol Rep. 2019 Mar;41(3):1455-1475. doi: 10.3892/or.2019.6956. Epub 2019 Jan 8.
The Hippo signaling pathway is considered to be a tissue growth regulator and tumor suppressor pathway that controls cell proliferation, differentiation, survival, regeneration and tissue homeostasis. Defects in Hippo kinases and hyperactivation of transcriptional co‑activator with PDZ‑binding motif and Yes‑associated protein (YAP) may contribute to the development of different types of cancer. The Hippo pathway is regulated in a variety of way, of which ubiquitination is of considerable importance. Ubiquitination is a crucial post‑translational protein modification in cancer cells and is an applicable target for pharmacological intervention. Ubiquitin modifications are involved in regulating various physiological processes and are counteracted by deubiquitination. Imbalanced ubiquitination‑deubiquitination is closely associated with tumor initiation and progression. Therefore, the examination of the specific association between the Hippo pathway and ubiquitination is of interest. The present study reviews the modulatory mechanism of ubiquitination‑deubiquitination in the Hippo signaling pathway, the recent progress in identifying therapeutic targets and strategies, and the future directions in the field that may contribute to better tumor diagnosis and treatment.
Hippo 信号通路被认为是一种组织生长调节剂和肿瘤抑制通路，可控制细胞增殖、分化、存活、再生和组织平衡。Hippo 激酶的缺陷和 PDZ 结合基序与 Yes 相关蛋白（YAP）的转录共激活因子的过度激活可能导致不同类型的癌症的发展。Hippo 通路受到多种方式的调节，其中泛素化具有相当重要的意义。泛素化是癌细胞中一种重要的翻译后蛋白修饰，是药理学干预的一个适用靶点。泛素修饰参与调节各种生理过程，并被去泛素化所拮抗。泛素化-去泛素化的失衡与肿瘤的发生和进展密切相关。因此，研究 Hippo 通路与泛素化之间的特定关联具有重要意义。本研究综述了泛素化-去泛素化在 Hippo 信号通路中的调节机制、鉴定治疗靶点和策略的最新进展，以及该领域的未来发展方向，可能有助于更好地进行肿瘤诊断和治疗。
