Decoding the link between WWOX and p53 in aggressive breast cancer

Cell Cycle. 2019 Jun;18(11):1177-1186. doi: 10.1080/15384101.2019.1616998. Epub 2019 May 16.

Abstract

Basal-like breast cancer (BLBC) and triple-negative breast cancer (TNBC) are aggressive forms of human breast cancer with poor prognosis and limited treatment response. Molecular understanding of BLBC and TNBC biology is instrumental to improve detection and management of these deadly diseases. Tumor suppressors WW domain-containing oxidoreductase (WWOX) and TP53 are altered in BLBC and in TNBC. Nevertheless, the functional interplay between WWOX and p53 is poorly understood. In a recent study by Abdeen and colleagues, it has been demonstrated that WWOX loss drives BLBC formation via deregulating p53 functions. In this review, we highlight important signaling pathways regulated by WWOX and p53 that are related to estrogen receptor signaling, epithelial-to-mesenchymal transition, and genomic instability and how they impact BLBC and TNBC development.

Keywords: BLBC; ER; TNBC; breast cancer; fragile site; genomic instability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genomic Instability
  • Humans
  • Neoplasm Invasiveness
  • Receptors, Estrogen / physiology
  • Signal Transduction / genetics
  • Tumor Suppressor Protein p53 / physiology*
  • Tumor Suppressor Proteins / physiology*
  • WW Domain-Containing Oxidoreductase / physiology*

Substances

  • Receptors, Estrogen
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • WW Domain-Containing Oxidoreductase
  • WWOX protein, human

Grants and funding

This work was supported by the FP7 Ideas: European Research Council [682118]; Israel Science Foundation [1574/15].