"Cells may also be rendered more motile via epigenetic reprogramming. Several relevant genes such as uPA
 and S100A4
 have altered epigenetic patterning in cancer cells, allowing cell morphology to be modified to a more metastatic-favourable state. What remains unknown is if epigenetic modifications and ischemia are linked in promoting tumour metastasis. "
[Show abstract][Hide abstract] ABSTRACT: DNA hypomethylation is an important epigenetic modification found to occur in many different cancer types, leading to the upregulation of previously silenced genes and loss of genomic stability. We previously demonstrated that hypoxia and hypoglycaemia (ischemia), two common micro-environmental changes in solid tumours, decrease DNA methylation through the downregulation of DNMTs in human colorectal cancer cells. Here, we utilized a genome-wide cross-platform approach to identify genes hypomethylated and upregulated by ischemia. Following exposure to hypoxia or hypoglycaemia, methylated DNA from human colorectal cancer cells (HCT116) was immunoprecipitated and analysed with an Affymetrix promoter array. Additionally, RNA was isolated and analysed in parallel with an Affymetrix expression array. Ingenuity pathway analysis software revealed that a significant proportion of the genes hypomethylated and upregulated were involved in cellular movement, including PLAUR and CYR61. A Matrigel invasion assay revealed that indeed HCT116 cells grown in hypoxic or hypoglycaemic conditions have increased mobility capabilities. Confirmation of upregulated expression of cellular movement genes was performed with qPCR. The correlation between ischemia and metastasis is well established in cancer progression, but the molecular mechanisms responsible for this common observation have not been clearly identified. Our novel data suggests that hypoxia and hypoglycaemia may be driving changes in DNA methylation through downregulation of DNMTs. This is the first report to our knowledge that provides an explanation for the increased metastatic potential seen in ischemic cells; i.e. that ischemia could be driving DNA hypomethylation and increasing expression of cellular movement genes.
PLoS ONE 07/2014; 9(7):e103243. DOI:10.1371/journal.pone.0103243 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The dependence of final vibrational action and collision time on the initial vibrational phase of H2 is examined on a model potential-energy surface (PES) for H2-W(001) collisions and it is shown that the switching region between the reactive and nonreactive bands is a fractal zone regardless of the details of the PES provided the dissociation probability is non-zero and less than unity.
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