Interplay between p53 and VEGF: how to prevent the guardian from becoming a villain.

摘要

Rapid tumor cell proliferation frequently outpaces adequate vascularization, resulting in a limited cellular oxygen supply. Low cellular oxygen, 'hypoxia' is often associated with necrotic tumor foci, but also with the selection of aggressive survival mutations. Interplay between tumor cells and the associated stroma (including endothelial cells) is critical in determining tumor progression.1 A rate-limiting 'angiogenic switch' in response to hypoxia promotes tumor vascularization. The consequence is a partial restoration of oxygen to the growing tumor edge and this is repeated with tumor expansion.2 The molecular processes mediating these transitions are of potential therapeutic relevance. Two pathways that are central to the hypoxic response in cancers are regulated by (1) the major tumor suppressor p53; and (2) the crucial modulator of new vasculature, 'neo-angiogenesis', vascular endothelial growth factor (VEGF). The study by Ghahremani et al.3 in CDD 2013 provides a new insight into the complex cross-talk between these two pathways under hypoxic conditions relevant to tumorigenesis. The consequences for tumor vascularization of disrupting these pathways, define the major novelty of this study, with important implications for p53-targeted anti-cancer therapy.