9 research outputs found
Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environment
Polysialic acid (polySia) is a unique carbohydrate polymer expressed on the surface of NCAM (neuronal cell adhesion molecule) in a number of cancers where it modulates cell-cell and cell-matrix adhesion, migration, invasion and metastasis and is strongly associated with poor clinical prognosis. We have carried out the first investigation into the effect of polySia expression on the behaviour of cancer cells in hypoxia, a key source of chemoresistance in tumours. The role of polysialylation and associated tumour cell migration and cell adhesion were studied in hypoxia, along with effects on cell survival and the potential role of HIF-1. Our findings provide the first evidence that polySia expression sustains migratory capacity and is associated with tumour cell survival in hypoxia. Initial mechanistic studies indicate a potential role for HIF-1 in sustaining polySia-mediated migratory capacity, but not cell survival. These data add to the growing body of evidence pointing to a crucial role for the polysialyltransferases (polySTs) in neuroendocrine tumour progression and provide the first evidence to suggest that polySia is associated with an aggressive phenotype in tumour hypoxia. These results have significant potential implications for polyST inhibition as an anti-metastatic therapeutic strategy and for targeting hypoxic cancer cells
Low dose radiation primed iNOS + M1macrophages modulate angiogenic programming of tumor derived endothelium
The mechanisms and significance of up‐regulation of RhoB expression by hypoxia and glucocorticoid in rat lung and A549 cells
Hypoxia induces apoptosis and autophagic cell death in human periodontal ligament cells through HIF
Mitochondrial Regulation of Cell Survival and Death During Low-Oxygen Conditions
Mitochondria can initiate cell death or activate genes that promote cell survival in response to low oxygen. The BCL-2 family of proteins regulate cell death in response to anoxia (0–0.5% O2). By contrast, under hypoxia (0.5–3% O2), mitochondrial oxidative stress activates hypoxia-inducible factors (HIFs) to promote cell survival. In this review, we discuss how mitochondria, BCL-2 proteins, and HIFs are crucial for cellular responses to low oxygen. Antioxid. Redox Signal. 11, 2673–2683