Dysregulation of the endothelial cellular response to oxidative stress in cancer

Molecular Carcinogenesis
F Houle, J Huot

Abstract

The traffic of molecules and cells across the vessel wall is gated by vascular endothelial cells. In accordance, these cells play an active role in regulating cardiovascular and systemic homeostasis and in modulating physiopathological processes such as inflammation. Dysfunction of the regulatory systems of the endothelium and its incapacity to efficiently deal with its physicochemical surrounding leads to disruption of endothelial integrity. For example, alterations of the selective endothelial cell permeability barrier are early events in the sequence of oxidative stress-mediated injury that may contribute to extravasation of circulating cancer cells. Several lines of evidence indicate that the regulation of the endothelial barrier is tightly regulated by activation of signaling pathways that converge on the regulation of actin cytoskeletal dynamics. In particular, the integrity of the endothelial layer in response to oxidative stress is tightly regulated by the balanced activation of the extracellular-signal regulated kinase (ERK) and the stress-activated protein kinase-2/p38 (SAPK2/p38) pathways. Activation of the SAPK2/p38 pathway is required to trigger actin polymerization, whereas activation of the ERK pathway by contrib...Continue Reading

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