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WDHD1 is essential for the survival of PTEN-inactive triple-negative breast cancer

Ayse Ertay1, Huiquan Liu2, Dian Liu2

  • 1Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK.

Cell Death & Disease
|November 22, 2020
PubMed

Insights

Triple-negative breast cancer (TNBC) is aggressive and hard to treat. Researchers found that WDHD1 is essential for PTEN-inactive TNBC survival, suggesting it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype lacking standard therapeutic targets.
  • Loss of phosphatase and tensin homologue (PTEN) expression is common in TNBC, correlating with poor prognosis.
  • Synthetic lethality offers a promising strategy for targeting cancers with specific genetic alterations.

Purpose of the Study:

  • To identify synthetic lethal interactions in PTEN-deficient TNBC.
  • To investigate the role of WDHD1 (WD repeat and high-mobility group box DNA-binding protein 1) in TNBC.
  • To evaluate WDHD1 as a potential therapeutic target or biomarker for TNBC.

Main Methods:

  • TCGA database analysis to assess gene expression in TNBC.
  • Whole-genome siRNA screening in PTEN-negative and -positive cells.
  • Validation of WDHD1 function in 2D and 3D cell cultures and patient samples.

Main Results:

  • WDHD1 expression is upregulated in PTEN-low TNBC samples.
  • WDHD1 knockdown significantly reduces viability in PTEN-negative TNBC cells.
  • WDHD1 plays a crucial role in mediating protein translation demands in PTEN-inactive TNBC.

Conclusions:

  • WDHD1 is essential for the survival of PTEN-inactive TNBC cells.
  • WDHD1 represents a potential synthetic lethal target for TNBC treatment.
  • WDHD1 may serve as a valuable biomarker for TNBC prognosis and therapeutic response.

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