ArticleJournal of cellular and molecular medicine2014
Elongation factor-2 kinase regulates TG2/β1 integrin/Src/uPAR pathway and epithelial-mesenchymal transition mediating pancreatic cancer cells invasion.
Article in Journal of cellular and molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 89 citations in OpenAlex.
- The Role of the TG2-GPR56 Complex in Cutaneous Squamous Cell Carcinoma (CSCC) Aggression and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- Novel PROTACs targeting tissue transglutaminase (TG2) suppress tumorigenicity of ovarian cancer cells.European journal of medicinal chemistry · 2026Article
- MMP-9 regulates disulphide isomerase activity of TGM2 to enhance fusion glycoprotein-mediated syncytium formation of respiratory syncytial virus.Protein & cell · 2026Article
- The cross-talk between GSK-3β, RKIP, and PTEN as potential targets for therapeutic implications in cancer: a comprehensive insight.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026Review
- eEF2K is a poor prognostic factor and novel molecular target in pancreatic cancer: regulating tumor growth and progression via the tumor microenvironment.Cell death & disease · 2025Article
- Pirfenidone alleviates fibrosis by acting on tumour-stroma interplay in pancreatic cancer.British journal of cancer · 2024Article
- Design and Characterization of a Novel eEF2K Degrader with Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- CaBiomolecules · 2023Review
- Sodium tanshinone IIA sulphate inhibits angiogenesis in lung adenocarcinoma via mediation of miR-874/eEF-2K/TG2 axis.Pharmaceutical biology · 2023Article
- Rottlerin and genistein inhibit neuroblastoma cell proliferation and invasion through EF2K suppression and related protein pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Functional roles of SRC signaling in pancreatic cancer: Recent insights provide novel therapeutic opportunities.Oncogene · 2023Review
- Article
- Novel etodolac derivatives as eukaryotic elongation factor 2 kinase (eEF2K) inhibitors for targeted cancer therapy.RSC medicinal chemistry · 2022Article
- Review
- SPOCK1 promotes metastasis in pancreatic cancer via NF-κB-dependent epithelial-mesenchymal transition by interacting with IκB-α.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- The Multifaceted Role of HSF1 in Pathophysiology: Focus on Its Interplay with TG2.International journal of molecular sciences · 2021Review
- Transglutaminase 2 promotes tumorigenicity of colon cancer cells by inactivation of the tumor suppressor p53.Oncogene · 2021Article
- Proteomics analysis reveals that the proto-oncogene eIF-5A indirectly influences the growth, invasion and replication of Toxoplasma gondii tachyzoite.Parasites & vectors · 2021Article
- Target-Driven Design of a Coumarinyl Chalcone Scaffold Based Novel EF2 Kinase Inhibitor Suppresses Breast Cancer GrowthACS pharmacology & translational science · 2021Article
- Progress in the Development of Eukaryotic Elongation Factor 2 Kinase (eEF2K) Natural Product and Synthetic Small Molecule Inhibitors for Cancer Chemotherapy.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma is one of the lethal cancers with extensive local tumour invasion, metastasis, early systemic dissemination and poorest prognosis. Thus, understanding the mechanisms regulating invasion/metastasis and epithelial-mesenchymal transition (EMT), is the key for developing effective therapeutic strategies for pancreatic cancer (PaCa). Eukaryotic elongation factor-2 kinase (eEF-2K) is an atypical kinase that we found to be highly up-regulated in PaCa cells. However, its role in PaCa invasion/progression remains unknown. Here, we investigated the role of eEF-2K in cellular invasion, and we found that down-regulation of eEF-2K, by siRNA or rottlerin, displays impairment of PaCa cells invasion/migration, with significant decreases in the expression of tissue transglutaminase (TG2), the multifunctional enzyme implicated in regulation of cell attachment, motility and survival. These events were associated with reductions in β1 integrin/uPAR/MMP-2 expressions as well as decrease in Src activity. Furthermore, inhibition of eEF-2K/TG2 axis suppresses the EMT, as demonstrated by the modulation of the zinc finger transcription factors, ZEB1/Snail, and the tight junction proteins, claudins. Importantly, while eEF-2K silencing recapitulates the rottlerin-induced inhibition of invasion and correlated events, eEF-2K overexpression, by lentivirus-based expression system, suppresses such rottlerin effects and potentiates PaCa cells invasion/migration capability. Collectively, our results show, for the first time, that eEF-2K is involved in regulation of the invasive phenotype of PaCa cells through promoting a new signalling pathway, which is mediated by TG2/β1 integrin/Src/uPAR/MMP-2, and the induction of EMT biomarkers which enhance cancer cell motility and metastatic potential. Thus, eEF-2K could represent a novel potential therapeutic target in pancreatic cancer.
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