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Karolina Pospiech1, Elzbieta Płuciennik1, Andrzej K Bednarek1

  • 1Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland.

Frontiers in Oncology
|September 14, 2018
PubMed

Insights

The WWOX tumor suppressor gene is frequently deleted in breast cancer. Loss of WWOX impacts hormone receptor status, DNA repair, and patient prognosis, highlighting its critical role in cancer development.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • The WWOX tumor suppressor gene, located at 16q23.1-23.2, is frequently deleted in breast cancer (BC), affecting up to 80% of cases.
  • WWOX alterations are among the most common genetic changes observed in breast cancer.
  • The WWOX gene encodes a protein with WW domains for protein-protein interactions and an SDR domain involved in ligand conversion, potentially steroids.

Purpose of the Study:

  • To review the current understanding of the WWOX tumor suppressor gene's role in breast cancer.
  • To explore WWOX's functions in cell proliferation, migration, and gene transcription.
  • To discuss WWOX's involvement in DNA damage response, repair pathways, and metabolic regulation in breast cancer.

Main Methods:

  • Literature review of studies investigating WWOX in breast cancer.
  • Analysis of WWOX expression, deletions, and protein interactions.
  • Examination of WWOX's role in cellular processes and patient outcomes.

Main Results:

  • Increased WWOX expression inhibits proliferation and tumor growth but enhances migration.
  • WWOX interacts with proteins like p73, AP-2γ, and ERBB4, modulating transcription.
  • WWOX influences hormone receptor status (ER, PR), DNA repair (ATM, Brca1-Wwox interaction), and glycolysis via HIF1α.

Conclusions:

  • WWOX plays a multifaceted role in breast cancer, influencing tumor suppression, hormone sensitivity, genomic stability, and metabolism.
  • Decreased WWOX expression is linked to poorer prognosis, including higher relapse and mortality rates.
  • Further research into WWOX's mechanisms and therapeutic potential in breast cancer is warranted.

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