Stathmin regulates mutant p53 stability and transcriptional activity in ovarian cancer

Stathmin is a p53‐target gene, frequently overexpressed in late stages of human cancer progression. Type II High Grade Epithelial Ovarian Carcinomas (HG‐EOC) represents the only clear exception to this observation. Here, we show that stathmin expression is necessary for the survival of HG‐EOC cells carrying a p53 mutant (p53 MUT ) gene. At molecular level, stathmin favours the binding and the phosphorylation of p53 MUT by DNA‐PK CS , eventually modulating p53 MUT stability and transcriptional activity. Inhibition of stathmin or DNA‐PK CS impaired p53 MUT –dependent transcription of several M phase regulators, resulting in M phase failure and EOC cell death, both in vitro and in vivo . In primary human EOC a strong correlation exists between stathmin, DNA‐PK CS , p53 MUT overexpression and its transcriptional targets, further strengthening the relevance of the new pathway here described. Overall our data support the hypothesis that the expression of stathmin and p53 could be useful for the identification of high risk patients that will benefit from a therapy specifically acting on mitotic cancer cells. Graphical Abstract In high‐grade epithelial ovarian carcinomas (the most lethal gynecological cancers), p53 gain‐offunction mutation is a driving oncogenic event. Here, Stathmin is shown to control p53 stability by modulating p53mut/DNA‐PK interaction.