Loss of p53 expression in cancer cells alters cell cycle response after inhibition of exportin-1 but does not prevent cell death.

ABSTRACT: The tumor suppressor protein p53 is central to the cellular stress response and may be a predictive biomarker for cancer treatments. Upon stress, wildtype p53 accumulates in the nucleus where it enforces cellular responses, including cell cycle arrest and cell death. p53 is so dominant in its effects, that p53 enforcement - or - restoration therapy is being studied for anti-cancer therapy. Two mechanistically distinct small molecules that act via p53 are the selective inhibitor of nuclear export, selinexor, and MDM2 inhibitor, nutlin-3a. Here, individual cells are studied to define cell cycle response signatures, which captures the variability of responses and includes the impact of loss of p53 expression on cell fates. The individual responses are then used to build the population level r

SUBMITTER: Marcus JM 

PROVIDER: S-EPMC6110605 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature