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Updated: Jan 13, 2026

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PCBP1 binding to single-stranded poly-cytosine motifs enhances cGAS sensing and impairs breast cancer development

Cécile Fréreux1, Joseph A Q Karam1, Breege V Howley1

  • 1Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.

Communications Biology
|January 7, 2026
PubMed

Insights

Poly(rC) Binding Protein 1 (PCBP1) acts as a tumor suppressor in breast cancer by enhancing the cGAS-STING pathway. This boosts anti-tumor immunity and improves patient survival.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is crucial for detecting cytosolic nucleic acids and initiating anti-tumor immune responses.
  • Dysregulation of this pathway is implicated in various cancers, including breast cancer, highlighting its therapeutic potential.

Purpose of the Study:

  • To investigate the role of Poly(rC) Binding Protein 1 (PCBP1) in breast cancer progression and its impact on the cGAS-STING pathway.
  • To elucidate the molecular mechanisms by which PCBP1 influences nucleic acid sensing and immune activation.

Main Methods:

  • Analysis of patient datasets to correlate PCBP1 expression with clinical outcomes.
  • Utilizing a transgenic mouse model with conditional PCBP1 knockout in mammary epithelial cells.
  • Biochemical assays to assess PCBP1's interaction with nucleic acids and its effect on cGAS activity.

Main Results:

  • PCBP1 expression inversely correlates with tumor burden and is associated with improved patient survival.
  • PCBP1 knockout leads to reduced type I Interferon production, decreased expression of Interferon Stimulated Genes, and diminished cytotoxic T cell infiltration.
  • PCBP1 binds to cytosine-rich single-stranded motifs, enhancing cGAS binding to nucleic acids and potentiating cGAS-STING pathway activation.

Conclusions:

  • PCBP1 functions as a tumor suppressor in breast cancer by amplifying cGAS-STING signaling.
  • PCBP1 acts as a nucleic acid co-sensor, enhancing the specificity and efficacy of cGAS-mediated immune surveillance.
  • Targeting PCBP1 or enhancing its function may represent a novel therapeutic strategy for breast cancer.

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