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Updated: Nov 2, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
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Published on: January 7, 2019

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FOXA1 overexpression suppresses interferon signaling and immune response in cancer

Yundong He1,2, Liguo Wang3, Ting Wei3

  • 1Department of Biochemistry and Molecular Biology.

The Journal of Clinical Investigation
|June 8, 2021
PubMed

Insights

Forkhead box A1 (FOXA1) overexpression hinders cancer immunotherapy by suppressing interferon signaling in prostate and breast cancers. Targeting FOXA1 may improve treatment response in these and other cancers.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Androgen receptor-positive prostate cancer (PCa) and estrogen receptor-positive breast cancer (BCa) exhibit limited immunotherapy responsiveness.
  • Mechanisms underlying this resistance are not fully understood.

Purpose of the Study:

  • To investigate the role of FOXA1 in mediating resistance to immunotherapy in PCa and BCa.
  • To explore FOXA1 as a potential therapeutic target.

Main Methods:

  • Correlation analysis of FOXA1 expression with interferon (IFN) signature and antigen presentation genes in patient data.
  • In vitro studies assessing FOXA1 binding to STAT2 and its effect on IFN signaling.
  • In vivo studies in mice and analysis of patient data to evaluate the impact of FOXA1 on therapeutic resistance.

Main Results:

  • FOXA1 overexpression inversely correlated with IFN signature and antigen presentation gene expression in PCa and BCa.
  • FOXA1 directly bound STAT2, suppressing its DNA-binding activity and IFN signaling.
  • Increased FOXA1 expression was linked to resistance to immunotherapy and chemotherapy in mice and patients, validated in bladder cancer.

Conclusions:

  • FOXA1 overexpression suppresses cancer immune response by inhibiting IFN signaling.
  • FOXA1 is a potential prognostic marker for therapy resistance in PCa, BCa, and bladder cancer.
  • Targeting FOXA1 could enhance sensitivity to immunotherapy and chemotherapy in these cancers.
Keywords:
CancerCancer immunotherapyCell BiologyMolecular biologyTherapeutics

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