NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China.
J Zhejiang Univ Sci B. 2024 Jul 15;25(7):541-556. doi: 10.1631/jzus.B2300457.
The protein kinase B (Akt) pathway can regulate the growth, proliferation, and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes, thus affecting the development and treatment of a range of diseases. Thioesterase superfamily member 4 (THEM4), a member of the thioesterase superfamily, is one of the Akt kinase-binding proteins. Some studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its phosphorylation. Initially, THEM4 was considered an endogenous inhibitor of Akt, which can inhibit the phosphorylation of Akt in diseases such as lung cancer, pancreatic cancer, and liver cancer, but subsequently, THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma, which contradicts previous findings. Considering these two distinct views, this review summarizes the important roles of THEM4 in the Akt pathway, focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases, especially cancer. This work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.
蛋白激酶 B（Akt）途径可通过激活多种下游靶基因来调节肿瘤细胞和干细胞的生长、增殖和代谢，从而影响多种疾病的发生和治疗。硫酯酶超家族成员 4（THEM4）是硫酯酶超家族的一员，是 Akt 激酶结合蛋白之一。一些关于癌症等疾病的机制研究表明，THEM4 与 Akt 结合以调节其磷酸化。最初，THEM4 被认为是 Akt 的内源性抑制剂，可抑制肺癌、胰腺癌和肝癌等疾病中 Akt 的磷酸化，但随后发现，THEM4 通过正向调节 Akt 活性在乳腺癌和鼻咽癌中促进肿瘤细胞的增殖，这与之前的发现相矛盾。考虑到这两种截然不同的观点，本综述总结了 THEM4 在 Akt 途径中的重要作用，重点介绍了 THEM4 作为 Akt 结合蛋白及其在各种疾病（尤其是癌症）中与 Akt 磷酸化的调节关系。这项工作为更好地理解 THEM4 与 Akt 结合在疾病治疗中的作用提供了依据。
