Impact of silencing eEF2K expression on the malignant properties of chordoma.

BACKGROUND: Eukaryotic elongation factor 2 kinase (eukaryotic elongation factor 2 kinase, eEF2K) is a calcium calmodulin dependent protein kinase that keeps the highest energy consuming cellular process of protein synthesis under check through negative regulation. eEF2K pauses global protein synthesis rates at the translational elongation step by phosphorylating its only kown substrate elongation factor 2 (eEF2), a unique translocase activity in ekaryotic cells enabling the polypeptide chain elongation. Therefore, eEF2K is thought to preserve cellular energy pools particularly upon acute development of cellular stress conditions such as nutrient deprivation, hypoxia, or infections. Recently, high expression of this enzyme has been associated with poor prognosis in an array of solid tumor types. Therefore, in a growing number of studies tremendous effort is being directed to the development of treatment methods aiming to suppress eEF2K as a novel therapeutic approach in the fight against cancer. METHODS: In our study, we aimed to investigate the changes in the tumorigenicity of chordoma cells in presence of gene silencing for eEF2K. Taking a transient gene silencing approach using siRNA particles, eEF2K gene expression was suppressed in chordoma cells. RESULTS: Silencing eEF2K expression was associated with a slight increase in cellular proliferation and a decrease in death rates. Furthermore, no alteration in the sensitivity of chordoma cells to chemotherapy was detected in response to the decrease in eEF2K expression which intriguingly promoted suppression of cell migratory and invasion related properties. CONCLUSION: Our findings indicate that the loss of eEF2K expression in chordoma cell lines results in the reduction of metastatic capacity.

Targeting Cancer Metabolism and Cell Cycle by Plant-Derived Compounds.

Cancer has an increasing death rate over the world population without discriminating between the industrial and developing countries. Complexity of cancer such as ability of cancer cells to develop resistance to drugs or differential behavior of sub-types and different responses from the patients indicate the continuous need for research and development of new anticancer drugs, new formulations of drug combinations and treatment strategies. Not too surprisingly nature itself, is often the largest territorial reservoir as a source for this type of research and development. Speaking of plant variety, more than 1000 plants have already been identified to produce agents with anticancer activities. In this review, a panel of plant derived anti-cancer agents will be reiterated in terms of their mechanism of action in treatment of disease.

NANOG Dominates Interleukin-6-Induced Sphere Formation in Prostate Cancer.

OBJECTIVE: Identifying the dynamics of prostate tumor aggressiveness is essential to find new therapeutics for the treatment. Cancer stem cells contribute to cancer progression by promoting tumor growth and metastasis, resisting treatment, and evading the immune system. Interleukin 6 (IL-6) is a pleiotropic cytokine that functions in inflammation, immune response, etc. However, dysregulated expression of IL-6 plays a pathological role in such conditions as cancer. In this study, we aimed to elucidate the effect of IL-6 on cancer stemness genes in prostate cancer cells. METHODS: Enrichment of stem-like cells was achieved through the formation of tumor spheres using the DU-145 cell line. Sphere formation was conducted in a medium supplemented with IL-6 and compared to a control group. The number of spheres was quantified, and the resulting pellet was collected for quantitative reverse transcription polymerase chain reaction analysis to assess the impact of IL-6 induction on the expression of stemness-related genes. RESULTS: Tumor sphere numbers and sizes increased in IL-6-induced environment. NANOG expression elevated in an IL-6-enriched environment compared to the nontreated spheres. Our results demonstrated that IL-6 induction in prostate tumor spheres upregulates NANOG gene expression. CONCLUSION: Inducing IL-6 in prostate tumor spheres stimulates stemness biomarker NANOG genes. NANOG may be suggested as a therapeutic target for metastatic prostate cancer.

E-cadherin might be a stage-dependent modulator in aggressiveness in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) pathology is known for its uncontrollable progress due to highly invasive characteristics and refractory behavior against existing chemotherapies. The aberrant expression of CDH1 (expresses the protein E-cadherin) is associated with increased overall survival in various cancers, however, E-cadherin expression in PDAC progression has remained elusive. We investigated the impact of exogenously elevated E-cadherin levels on the tumorigenicity of transduced low grade and metastatic PDAC cell lines, Panc-1 and AsPC-1, respectively. Constitutive expression of E-cadherin promoted a more hybrid E/M state in AsPC-1 cells, while it was associated with the acquisition of a more epithelial-like state in Panc1 cells. Our study suggests that E-cadherin may play differential roles in determining the metastatic characteristics of primary and metastatic pancreatic cancer cells.