Roles of THEM4 in the Akt pathway: a double-edged sword

Wen XIE; Weidong LIU; Lei WANG; Bin ZHU; Cong ZHAO; Ziling LIAO; Yihan LI; Xingjun JIANG; Jie LIU; Caiping REN

doi:10.1631/jzus.B2300457

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Review | Updated：2024-07-17

Roles of THEM4 in the Akt pathway: a double-edged sword
Roles of THEM4 in the Akt pathway: a double-edged sword
THEM4在Akt通路中的作用：一把双刃剑
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 25, Issue 7, Pages: 541-556(2024)
Affiliations：

1.NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China
2.National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
3.The Key Laboratory of Carcinogenesis and Cancer Invasion of the Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha 410078, China
4.Department of Critical Care Medicine, Hainan Hospital of Chinese PLA General Hospital, Hainan Province Clinical Medical Center, Sanya 572013, China
Funds：
DOI：10.1631/jzus.B2300457
CLC：
CSTR：
Published： 15 July 2024 ，

Received： 26 June 2023 ，

Revised： 10 October 2023 ，
Accepted：

谢雯,刘卫东,王磊等.THEM4在Akt通路中的作用：一把双刃剑[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(07):541-556.

Wen XIE, Weidong LIU, Lei WANG, et al. Roles of THEM4 in the Akt pathway: a double-edged sword. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(7):541-556(2024)
谢雯,刘卫东,王磊等.THEM4在Akt通路中的作用：一把双刃剑[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(07):541-556. DOI： 10.1631/jzus.B2300457.

Wen XIE, Weidong LIU, Lei WANG, et al. Roles of THEM4 in the Akt pathway: a double-edged sword. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(7):541-556(2024) DOI： 10.1631/jzus.B2300457.

摘要

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。

Abstract

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.

关键词

蛋白激酶B（Akt）硫酯酶超家族成员4（THEM4）肿瘤增殖肿瘤转移

Keywords

Protein kinase B (Akt)Thioesterase superfamily member 4 (THEM4)Tumor proliferationTumor metastasis

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Related Institution

College of Pharmaceutical Science, Zhejiang University

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Department of Physiology, Zhejiang Medical College

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