Oxygen-generated spatial distribution of cell population links to p53 status

Low oxygen induces wild type p53 inactivation and selects for mutant-like p53 phenotypes for aggressive tumor growth. Recently, we have shown wild type p53 as a cellular oxygen-sensor that operates in switch-like fashion to transform its characters of a tumor suppressor or promoter in a gradient of hypoxia. However, it is unclear how hypoxic tumors select for wild type p53 phenotypes for oxygen-sensitive responses. Here, we show that oxygen-generated spatial distribution of the cell population induces p53 phenotype-specific survival or death. We have found that a dynamic state of spatial scatters or clustering patterns of cell populations favor the survival of wild type more than the mutant phenotypes in a wide range of oxygen fluctuation by affecting p53 subcellular localization. Our results demonstrate how spatial distribution could function to establish wild type p53-mediated oxygen sensing and cell fate decisions in a cell population with heterogeneous p53 allele status. We anticipate that such behavior of cells in a gradient of oxygen can be utilized by the hypoxic tumors to maintain distinct p53 alleles and determine the release and metastasis of single or clustered circulating tumor cells (CTCs). Summary sentenceOxygen variation results in p53 phenotype-specific cell fate via the spatial distribution pattern of the cell population