What is the impact of eukaryotic elongation factor 2 kinase on cancer: A systematic review

Eukaryotic elongation factor 2 kinase (eEF-2K) is known as calcium/calmodulin-dependent protein kinase III and identified as a calcium/calmodulin (Ca²⁺/CaM)-dependent protein kinase (CaM-PK) that phosphorylates its only substrate eukaryotic elongation factor-2 (eEF-2) and blocks the ability of eEF-2 to bind the ribosome and translation elongation and inhibits global protein synthesis. The activators of eEF-2K include allosteric activator Ca/CaM, Ca/CaM-independent activator cAMP-dependent protein kinase (PKA) and H⁺. On the other hand, eEF-2K is inactivated by the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. However, the role of eEF-2K in cancer is not well understood. To provide opinion for the diagnosis and treatment of cancer, we summarized the role of eEF-2K in cancer. Based on the fundamental research on eEF-2K, scientists further investigated the role of eEF-2K in cancer and have reported its different effects in many kinds of cancer. eEF-2K involves in many signal pathways, including proliferation, apoptosis, autophagy, invasion and glycolysis, and promotes the development of cancer as an oncogene. Inhibition of eEF-2K by eEF-2K siRNA and little molecular inhibitors resulted in the suppression of proliferation, autophagy, invasion and glycolysis, and accelerate apoptosis to play an antitumor role. In this review, we summarize the regulation and role of eEF-2K in cancer as an oncogene and the exploitation of the inhibitor of eEF-2K. Combined treatment of eEF-2K inhibitor and chemotherapeutics should be a potential tool in cancer therapy.