Thromboxane A2 receptor (TBXA2R) is a potent survival factor for triple negative breast cancers (TNBCs)

Katy Orr1, Niamh E Buckley1, Paula Haddock1

  • 1Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.

Oncotarget
|August 4, 2016
PubMed

Insights

Thromboxane A2 receptor (TBXA2R) is elevated in good-outcome Triple Negative Breast Cancer (TNBC). Targeting TBXA2R shows promise for treating TNBC by inhibiting cell survival and migration.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Triple Negative Breast Cancer (TNBC) presents the poorest clinical outcomes among breast cancer subtypes.
  • TNBC is characterized by the absence of Estrogen Receptor alpha (ERα), Progesterone Receptor (PR), and Human Epidermal growth factor Receptor 2 (HER2) expression.
  • Identifying novel therapeutic targets is crucial for improving TNBC patient prognosis.

Purpose of the Study:

  • To identify genes that drive proliferation and/or survival in TNBC.
  • To discover potential novel therapeutic targets for TNBC treatment.

Main Methods:

  • Microarray profiling of primary TNBC samples.
  • Differential gene expression analysis based on clinical outcomes (relapse within 3 years vs. no relapse > 3 years) after FEC chemotherapy.
  • Investigated the role of Thromboxane A2 receptor (TBXA2R) in TNBC cell lines, including knockdown experiments and analysis of its regulation by BRCA1 and c-Myc.

Main Results:

  • Elevated TBXA2R expression was observed in TNBCs with a good clinical outcome.
  • TBXA2R knockdown led to significant cell killing in TNBC cell lines.
  • TBXA2R expression is upregulated by BRCA1 knockdown, with c-Myc mediating this transcriptional repression.
  • TBXA2R promotes TNBC cell migration, invasion, and activates Rho signaling, which can be inhibited by ROCK inhibitors.
  • TBXA2R confers resistance to DNA damage by reducing reactive oxygen species levels.

Conclusions:

  • TBXA2R is a novel gene associated with breast cancer, essential for the survival and migration of a subset of TNBC.
  • TBXA2R represents a potential therapeutic target for developing more effective treatments for Triple Negative Breast Cancer.

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