Somatic loss of WWOX is associated with TP53 perturbation in basal-like breast cancer

Suhaib K. Abdeen, Uri Ben-David, Aya Shweiki, Bella Maly, Rami I. Aqeilan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Inactivation of WW domain-containing oxidoreductase (WWOX), the gene product of the common fragile site FRA16D, is a common event in breast cancer and is associated with worse prognosis of triple-negative breast cancer (TNBC) and basal-like breast cancer (BLBC). Despite recent progress, the role of WWOX in driving breast carcinogenesis remains unknown. Here we report that ablation of Wwox in mammary tumor-susceptible mice results in increased tumorigenesis, and that the resultant tumors resemble human BLBC. Interestingly, copy number loss of Trp53 and downregulation of its transcript levels were observed in the Wwox knockout tumors. Moreover, tumors isolated from Wwox and Trp53 mutant mice were indistinguishable histologically and transcriptionally. Finally, we find that deletion of TP53 and WWOX co-occurred and is associated with poor survival of breast cancer patients. Altogether, our data uncover an essential role for WWOX as a bona fide breast cancer tumor suppressor through the maintenance of p53 stability.

Original languageAmerican English
Article number832
JournalCell Death and Disease
Volume9
Issue number8
DOIs
StatePublished - 1 Aug 2018

Bibliographical note

Funding Information:
The Aqeilan lab is supported by European Research Council (ERC)-Consolidator Grant under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 682118) and Israel Science Foundation (grant agreement No 1574/15).

Publisher Copyright:
© 2018, The Author(s).

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