Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.13.3 (histidine kinase)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant melanoma exhibits a distinct metabolic phenotype with high glycolytic activity. Previously, we have shown that glucose transporter isoform 1 (GLUT1) favors growth and metastasis of malignant melanoma. In this study, we investigated the expression of GLUT1 and the further glycolysis-related genes hexokinase 1 and 2 (HK1, HK2), lactate dehydrogenase A (LDH-A) and monocarboxylate transporters 1 and 4 (MCT1, MCT4) in eleven human melanoma cell lines under normoxic and hypoxic conditions. Furthermore, a set of 25 human malignant melanoma tissue samples was analyzed. Under hypoxic conditions, we could observe a significant upregulation of hypoxia-inducible factor 1 alpha (HIF-1a) target genes GLUT1, HK2 and LDH-A, but not MCT4. While under normoxic conditions the expression of glycolysis-related genes showed no correlation with origin or BRAF mutation status, GLUT1 expression was significantly elevated in metastatic and BRAF-V600E mutated melanoma cell lines under hypoxic conditions. Furthermore, GLUT1 expression in human melanoma tissue samples correlated significantly with HK1, LDH-A and MCT1 expression, confirming a glycolytic phenotype. Notably, Cyclin D1 expression, which is used as a prognostic marker for the outcome of melanoma patients, as it is associated with proliferation and invasiveness of melanoma, significantly correlated with GLUT1, HK1, LDH-A and MCT1 expression. In summary, our findings provide further evidence that enhanced glycolytic activity in melanoma favors disease progression and is an attractive therapeutic target for this highly aggressive tumor.
 ...
PMID:Characterization of glycolysis-related gene expression in malignant melanoma. 3179 1

Papillary renal cell carcinoma (pRCC) is characterized with underlying genetic disorders and the role enolase 2 (ENO2) in ccRCC is unknown. An in silico exploratory analysis using multiple public genetic datasets was used to establish association between ENO2 expression and clinicopathological parameters. Associations of interest were validated using 49 pRCC samples using immunohistochemistry. In vitro and in vivo assays were carried out to validate findings in tissue. ENO2 was overexpressed and prognostic in pRCC. ENO2 expression was significantly higher in younger patients and in CpG island methylator phenotype subtype. ENO2-overexpressed cases showed significant enrichment in glycolysis. Overexpression of ENO2 significantly increased proliferation and silencing of ENO2 significantly inhibited growth of ACHN cells. Glycolytic genes HK1, HK 2, and lactate dehydrogenase A were decreased when ENO2 was silenced in ACHN. Glycolytic inhibitor TT-232 showed minimal inhibitory effect on ACHN cells yet showed synergistic effect in the presence of ENO2 silencing. ENO2 significantly increased and decreased extracellular glucose, respectively in ACHN cells. Xenograft mouse model showed ENO2 silencing and TT-232 combination treatment showed synergistic effect in ACHN tumors. ENO2 is associated with worsened prognosis in pRCC and is related to glycolysis. ENO2-targeted therapy can be of therapeutic potential.
 ...
PMID:Overexpression of enolase 2 is associated with worsened prognosis and increased glycikolysis in papillary renal cell carcinoma. 3313 64