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Targeting TAF1 with BAY-299 induces antitumor immunity in triple-negative breast cancer

Sheyu Zhang1, Xueying Liu2, Wenjun Chen2

  • 1Tianjin University, School of Pharmaceutical Science and Technology, Tianjin, China.

Biochemical and Biophysical Research Communications
|May 6, 2023
PubMed

Insights

Targeting TATA-box binding protein associated factor 1 (TAF1) in triple-negative breast cancer (TNBC) induces antiviral responses and suppresses growth. However, high proliferating cell nuclear antigen (PCNA) levels may limit treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its heterogeneity, poor prognosis, and limited therapeutic strategies.
  • TATA-box binding protein associated factor 1 (TAF1) plays a crucial role in transcriptional regulation, implicating it in cancer progression, yet its therapeutic targeting in TNBC is unexplored.

Purpose of the Study:

  • To investigate the therapeutic potential and underlying mechanisms of TAF1 inhibition in triple-negative breast cancer.
  • To identify predictive biomarkers for TAF1 inhibition response in TNBC.

Main Methods:

  • Utilized the chemical probe BAY-299 to inhibit TAF1 in TNBC models.
  • Analyzed gene expression, endogenous retrovirus (ERV) induction, double-stranded RNA (dsRNA) formation, and interferon responses.
  • Integrated transcriptome and proteome data from TNBC cell lines and patient datasets, including proliferating cell nuclear antigen (PCNA) analysis.

Main Results:

  • TAF1 inhibition triggered endogenous retrovirus expression and double-stranded RNA accumulation, activating interferon responses and suppressing cell growth in a subset of TNBC.
  • This TAF1-interferon axis correlation was confirmed across independent patient cohorts.
  • Heterogeneous responses to TAF1 inhibition were observed, with high proliferating cell nuclear antigen (PCNA) protein levels identified as a potential biomarker for suppressed anti-tumor immunity and limited treatment efficacy.

Conclusions:

  • TAF1 inhibition can induce an anti-viral mimicry response, leading to growth suppression in specific TNBC subtypes.
  • The study validates the link between TAF1 and interferon signaling in breast cancer.
  • Proliferating cell nuclear antigen (PCNA) serves as a predictive biomarker, highlighting potential limitations of TAF1 inhibition in tumors with suppressed immune microenvironments.
Keywords:
Immune responsePCNATAF1TNBCTumor inhibitiondsRNA

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