Role of ARK5 in cancer and other diseases (Review).

Abstract

Malignant tumors are often exposed to hypoxic and glucose-starved microenvironments. AMP-activated protein kinase (AMPK) is an energy sensor that is stimulated during energy-deficient conditions and protects cells from hypoxic injury by regulating metabolism. AMPK-related protein kinase 5 (ARK5) is a member of the catalytic sub-unit of the AMPK family and has an important role in energy regulation and hypoxia. ARK5 is regulated by Akt and liver kinase B1 and is associated with numerous tumor-related molecules to exert the negative effects of tumors. Studies have revealed ARK5 overexpression in cases of tumor invasion and metastasis and a positive association with the degree of cancer cell malignancy, which is regarded as a key element in determining cancer prognosis. Furthermore, ARK5 downregulation improves drug sensitivity through the epithelial-mesenchymal transition pathway, indicating that it may be a potential therapeutic target. In other non-cancer conditions, ARK5 has various roles in neurodegenerative diseases (Alzheimer's and Huntington's disease), renal disorders (diabetic nephropathy and renal fibrosis) and physiological processes (striated muscle generation). In the present review, the upstream and downstream molecular pathways of ARK5 in cancer and other diseases are described and potential therapeutic strategies are discussed.