title: Tumor suppressor p53 stole the AKT in hypoxia.
abstract: The presence of hypoxia within a tumor is associated with poor clinical outcome, which is often exacerbated by loss of the tumor suppressor p53. In the presence of functional p53, hypoxic conditions promote apoptosis; however, the p53-dependent genes that mediate this process are not well understood. In this issue of the JCI, Leszczynska and colleagues identify a p53-dependent six-gene signature that is specifically induced in hypoxia and mediates apoptosis. In patients with a variety of cancers, downregulation of this gene signature was associated with poor clinical outcome. Induction of p53-dependent apoptosis under hypoxia was mediated by AKT inhibition, and treatment with the combination of an AKT inhibitor and ionizing radiation decreased tumor size in a p53-deficient xenograft model more substantially than either single-agent treatment. The results of this study provide important insight into p53-mediated apoptosis under hypoxia and suggest that AKT inhibition has therapeutic potential for inducing apoptosis in hypoxic, p53-deficient cancers.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Yun
authors.forename: Peter M
authors.initials: PM
authors.lastname: Glazer
mesh_terms: D017209:Apoptosis; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011836:Radiation Tolerance; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt