%0 Journal Article
%T Roles of THEM4 in the Akt pathway: a double-edged sword.
%A Xie W
%A Liu W
%A Wang L
%A Zhu B
%A Zhao C
%A Liao Z
%A Li Y
%A Jiang X
%A Liu J
%A Ren C
%J J Zhejiang Univ Sci B
%V 25
%N 7
%D 2024 Jul 15
%M 39011675
%F 5.552
%R 10.1631/jzus.B2300457
%X 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.<BR>蛋白激酶B（Akt）通路可通过激活下游多个靶基因来调控肿瘤细胞和干细胞的生长、增殖和代谢等，从而影响一系列疾病的发生和治疗。硫酯酶超家族成员4（THEM4）作为硫酯酶超家族成员中的一员，也是Akt激酶的结合蛋白之一。癌症等疾病的机制研究发现THEM4可以与Akt结合从而调控Akt的磷酸化。最初，THEM4被认为是Akt的内源性抑制剂，在肺癌、胰腺癌和肝癌等疾病中抑制Akt的磷酸化。但随后的研究发现，THEM4在乳腺癌和鼻咽癌中通过正向调节Akt活性促进肿瘤细胞的增殖，这与之前的研究结果正好相反。面对这两种截然不同的观点，本文综述了THEM4在Akt通路中的重要作用，重点探讨了THEM4作为一种Akt结合蛋白，在各种疾病（尤其是癌症）中与Akt磷酸化的调控关系。这将有助于更好地了解THEM4联合Akt在疾病治疗中的作用。.