PMID- 32377852 OWN - NLM STAT- MEDLINE DCOM- 20210607 LR - 20220623 IS - 1432-1440 (Electronic) IS - 0946-2716 (Linking) VI - 98 IP - 6 DP - 2020 Jun TI - Eukaryotic elongation factor-2 kinase (eEF2K) signaling in tumor and microenvironment as a novel molecular target. PG - 775-787 LID - 10.1007/s00109-020-01917-8 [doi] AB - Eukaryotic elongation factor-2 kinase (eEF2K), an atypical member of alpha-kinase family, is highly overexpressed in breast, pancreatic, brain, and lung cancers, and associated with poor survival in patients. eEF2K promotes cell proliferation, survival, and aggressive tumor characteristics, leading to tumor growth and progression. While initial studies indicated that eEF2K acts as a negative regulator of protein synthesis by suppressing peptide elongation phase, later studies demonstrated that it has multiple functions and promotes cell cycle, angiogenesis, migration, and invasion as well as induction of epithelial-mesenchymal transition through induction of integrin beta1, SRC/FAK, PI3K/AKT, cyclin D1, VEGF, ZEB1, Snail, and MMP-2. Under stress conditions such as hypoxia and metabolic distress, eEF2K is activated by several signaling pathways and slows down protein synthesis and helping cells to save energy and survive. In vivo therapeutic targeting of eEF2K by genetic methods inhibits tumor growth in various tumor models, validating it as a potential molecular target. Recent studies suggest that eEF2K plays a role in tumor microenvironment cells by monocyte chemoattractant protein-1 (MCP-1) and accumulation of tumor-associated macrophages. Due to its clinical significance and the pivotal role in tumorigenesis and progression, eEF2K is considered as an important therapeutic target in solid tumors. However, currently, there is no specific and potent inhibitor for translation into clinical studies. Here, we aim to systematically review current knowledge regarding eEF2K in tumor biology, microenvironment, and development of eEF2K targeted inhibitors and therapeutics. FAU - Karakas, Didem AU - Karakas D AD - Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Istinye University, Istanbul, Turkey. FAU - Ozpolat, Bulent AU - Ozpolat B AUID- ORCID: 0000-0003-1190-9255 AD - Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. bozpolat@mdanderson.org. LA - eng PT - Journal Article PT - Review DEP - 20200507 PL - Germany TA - J Mol Med (Berl) JT - Journal of molecular medicine (Berlin, Germany) JID - 9504370 RN - 0 (Biomarkers, Tumor) RN - 0 (Protein Kinase Inhibitors) RN - 0 (RNA, Untranslated) RN - EC 2.7.1.17 (EEF2K protein, human) RN - EC 2.7.11.20 (Elongation Factor 2 Kinase) SB - IM MH - Animals MH - Apoptosis MH - Autophagy MH - Biomarkers, Tumor MH - Disease Susceptibility MH - Elongation Factor 2 Kinase/antagonists & inhibitors/chemistry/genetics/*metabolism MH - Enzyme Activation MH - Gene Expression MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Molecular Targeted Therapy MH - Neoplasms/drug therapy/*etiology/*metabolism/pathology MH - Protein Conformation MH - Protein Kinase Inhibitors/chemistry/pharmacology MH - RNA, Untranslated/genetics MH - *Signal Transduction MH - Structure-Activity Relationship MH - *Tumor Microenvironment/drug effects/genetics OTO - NOTNLM OT - Eukaryotic elongation factor-2 kinase OT - Gene regulation OT - Protein synthesis OT - Therapy OT - Tumor microenvironment OT - eEF2K EDAT- 2020/05/08 06:00 MHDA- 2021/06/08 06:00 CRDT- 2020/05/08 06:00 PHST- 2019/03/13 00:00 [received] PHST- 2020/04/28 00:00 [accepted] PHST- 2020/04/26 00:00 [revised] PHST- 2020/05/08 06:00 [pubmed] PHST- 2021/06/08 06:00 [medline] PHST- 2020/05/08 06:00 [entrez] AID - 10.1007/s00109-020-01917-8 [pii] AID - 10.1007/s00109-020-01917-8 [doi] PST - ppublish SO - J Mol Med (Berl). 2020 Jun;98(6):775-787. doi: 10.1007/s00109-020-01917-8. Epub 2020 May 7.