Acylglycerol Kinase-Targeted Therapies in Oncology.

Binxiang Chu,Zhenghua Hong,Xiaohe Zheng

doi:10.3389/fcell.2021.659158

Binxiang Chu, Zhenghua Hong + Show 1 more

Open Access

https://doi.org/10.3389/fcell.2021.659158

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Abstract

Acylglycerol kinase (AGK) is a recently discovered mitochondrial lipid kinase, and mutation of its gene is the fundamental cause of Sengers syndrome. AGK is not only involved in the stability of lipid metabolism but also closely related to mitochondrial protein transport, glycolysis, and thrombocytopoiesis. Evidence indicates that AGK is an important factor in the occurrence and development of tumors. Specifically, AGK has been identified as an oncogene that partakes in the regulation of tumor cell growth, invasion, metastasis, and drug resistance. The versatility of AGK and its unique role in different types of cancerous and normal cells greatly piqued our interest. We believe that AGK is a promising target for cancer therapy. Therefore, this review summarizes the main research advances concerning AGK, including the discovery of its physiological/pathogenic mechanisms, and provides a reference for the feasible evaluation of AGK as a therapeutic target for human diseases, particularly tumors.

Highlights

Acylglycerol kinase (AGK), named multi-substrate lipid kinases (MULK), was initially found through its mutation in Sengers syndrome (Mayr et al, 2012)
We were surprised to find that a newly published study drew the mitochondrial proteome map of fibroblasts from patients with Sengers syndrome by using the quantitative proteomics method and found that the enzymes related to mitochondrial carbon metabolism were downregulated, which was detected in AGK-deficient cell lines (Jackson et al, 2021). These results suggest that the imbalance of carbon metabolism may be involved in the mitochondrial dysfunction associated with AGK deficiency, which provides a new insight for us to understand mitochondrial diseases, AGK mutation is the root cause of Sengers syndrome
Due to the heterogeneity and genetic instability of cancer, AGK seems to play a core role in cancer progression through different signaling pathways and molecules, such as the Hippo-Yes-associated protein 1 (YAP1), JAK2/STAT3, nuclear factor-kappa B (NF-κB), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways as well as the forkhead box O1 (FOXO1) and epidermal growth factor (EGF) transcription factors (Figure 7)

Summary

Introduction

Acylglycerol kinase (AGK), named multi-substrate lipid kinases (MULK), was initially found through its mutation in Sengers syndrome (Mayr et al, 2012). AGK is a nuclear gene-encoded protein mainly located in the mitochondrial membrane, while very recent studies suggest that a portion of AGK is localized elsewhere in the cell (Hu et al, 2019; Jiang et al, 2020).

Results

Conclusion