Stathmin regulates mutant p53 stability and transcriptional activity in ovarian cancer

Maura Sonego, Monica Schiappacassi, Sara Lovisa, Alessandra Dall'Acqua, Marina Bagnoli, Francesca Lovat, Massimo Libra, Sara D'Andrea, Vincenzo Canzonieri, Loredana Militello, Marco Napoli, Giorgio Giorda, Barbara Pivetta, Delia Mezzanzanica, Mattia Barbareschi, Barbara Valeri, Silvana Canevari, Alfonso Colombatti, Barbara Belletti, Giannino Del SalGustavo Baldassarre

Research output: Contribution to journalArticlepeer-review

Abstract

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 (p53MUT) gene. At molecular level, stathmin favours the binding and the phosphorylation of p53MUT by DNA-PKCS, eventually modulating p53MUT stability and transcriptional activity. Inhibition of stathmin or DNA-PKCS impaired p53MUT-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-PKCS, p53MUT 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.

Original languageEnglish
Pages (from-to)707-722
Number of pages16
JournalEMBO Molecular Medicine
Volume5
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • Carboplatinum
  • DNA-PK
  • Mutant p53
  • Ovarian cancer
  • Stathmin

ASJC Scopus subject areas

  • Molecular Medicine

Fingerprint Dive into the research topics of 'Stathmin regulates mutant p53 stability and transcriptional activity in ovarian cancer'. Together they form a unique fingerprint.

Cite this