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

Wen Xie1,2,3, Weidong Liu1,2,3, Lei Wang1,2,3

  • 1NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.

Journal of Zhejiang University. Science. B
|July 16, 2024
PubMed

Insights

Thioesterase superfamily member 4 (THEM4) interacts with the Akt pathway, showing dual roles in cancer. This review clarifies THEM4

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • The Akt (protein kinase B) pathway is crucial for regulating tumor cell growth, proliferation, and metabolism.
  • Thioesterase superfamily member 4 (THEM4) is identified as an Akt kinase-binding protein.
  • THEM4's role in Akt phosphorylation has yielded contradictory findings in various cancers.

Purpose of the Study:

  • To review and synthesize the current understanding of THEM4's function within the Akt pathway.
  • To elucidate the complex regulatory relationship between THEM4 and Akt phosphorylation across different diseases, particularly cancer.
  • To provide insights into the therapeutic implications of THEM4-Akt interactions.

Main Methods:

  • Literature review of existing studies on THEM4 and the Akt pathway.
  • Analysis of THEM4's binding mechanism with Akt.
  • Examination of THEM4's impact on Akt phosphorylation in various cancer models.

Main Results:

  • THEM4 exhibits opposing roles: initially described as an Akt inhibitor in lung, pancreatic, and liver cancers.
  • Later studies indicate THEM4 promotes tumor cell proliferation by activating Akt in breast and nasopharyngeal carcinomas.
  • These conflicting results highlight the context-dependent nature of THEM4's function in cancer.

Conclusions:

  • THEM4 acts as a key modulator of the Akt pathway with context-specific effects on cancer progression.
  • Understanding the dual role of THEM4 in Akt regulation is essential for developing targeted cancer therapies.
  • Further research is warranted to fully delineate THEM4's mechanisms and therapeutic potential in conjunction with Akt.
Keywords:
Protein kinase B (Akt)Thioesterase superfamily member 4 (THEM4)Tumor metastasisTumor proliferation

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