Proceedings of the National Academy of Sciences · 2014 · 59 citations · 32 references
MedicineCancer BiologyOncologyMetastasisMolecular OncologyOncogenesAngiogenesisAngiogenesis In CancerCancer Cell SignalingCancer ProgressionOncogenic Signaling PathwaysTumor Suppressor GenesAngiogenic CytokinesAngiogenic ModulationProangiogenic CytokinesTumor Angiogenesis SignalingTumor Suppressor LossTumor Suppressor NetworksTumor Suppressor PathwaysTumor-associated Cytokines
The p53-family member TAp73 is known to function as a tumor suppressor and regulates genomic integrity, cellular proliferation, and apoptosis; however, its role in tumor angiogenesis is poorly understood. Here we demonstrate that TAp73 regulates tumor angiogenesis through repression of proangiogenic and proinflammatory cytokines. Importantly, loss of TAp73 results in highly vascularized tumors, as well as an increase in vessel permeability resulting from disruption of vascular endothelial-cadherin junctions between endothelial cells. In contrast, loss of the oncogenic p73 isoform ΔNp73 leads to reduced blood vessel formation in tumors. Furthermore, we show that up-regulated ΔNp73 levels are associated with increased angiogenesis in human breast cancer and that inhibition of TAp73 results in an accumulation of HIF-1α and up-regulation of HIF-1α target genes. Taken together, our data demonstrate that loss of TAp73 or ΔNp73 up-regulation activates the angiogenic switch that stimulates tumor growth and progression.
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Comprehensive molecular portraits of human breast tumours
The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice
Jerry M. Adams, A. W. Harris, Carl A. Pinkert et al. · Nature · 1985 · 1.8K citations