Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome

摘要: The p53 tumor suppressor protein has long been recognized as the central factor protecting humans from cancer. It famously dubbed “the guardian of genome” due to its ability respond genotoxic stress, such DNA damage and other stress signals, protect genome by inducing a variety biological responses including repair, cell cycle arrest, apoptosis. However, suppressive effects go far beyond roles in mediating these three processes. There is growing evidence that also exerts on multiple aspects formation, suppression metastasis and, summarized this review, inhibition new blood vessel development (angiogenesis). shown limit angiogenesis at least mechanisms: (1) interfering with regulators hypoxia mediate angiogenesis, (2) inhibiting production proangiogenic factors, (3) directly increasing endogenous inhibitors. combination allows efficiently shut down angiogenic potential cancer cells. Inactivation p53, which occurs approximately half all tumors, reverses effects; consequence, tumors carrying mutations appear more vascularized are often aggressive correlate poor prognosis for treatment. Thus, loss functional during tumorigenesis likely represents an essential step switch phenotype displayed tumors.