Tumor suppression by p53 is mediated in part by the antiangiogenic activity of endostatin and tumstatin.
Recent research shows that p53 suppresses tumor angiogenesis by transcriptionally activating the alpha(II) collagen prolyl-4-hydroxylase gene. This results in the extracellular release of the potent endogenous angiogenesis inhibitors endostatin and tumstatin from collagens 18 and 4, respectively. The involvement of these inhibitors elucidates a molecular mechanism. By simultaneously repressing a multitude of proangiogenic pathways and by inducing antiangiogenic pathways, a tumor suppressor protein can prevent an incipient tumor from switching to the angiogenic phenotype. Thus, p53 guards the genome from cancer by controlling the three fundamental processes that are critical for growth of a primary tumor and its metastases-tumor cell proliferation, apoptosis, and tumor angiogenesis.
Folkman
Judah
J
Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. judah.folkman@childrens.harvard.edu
D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D024141:Collagen Type IV / Q000378:metabolism*; D043170:Collagen Type XVIII / Q000378:metabolism; D043169:Endostatins / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D001324:Autoantigens; D024141:Collagen Type IV; D043170:Collagen Type XVIII; D043169:Endostatins; D016159:Tumor Suppressor Protein p53; C057112:type IV collagen alpha3 chain; D011393:Procollagen-Proline Dioxygenase