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PRMT1 Regulates EGFR and Wnt Signaling Pathways and Is a Promising Target for Combinatorial Treatment of Breast

Samyuktha Suresh1, Solène Huard1, Amélie Brisson1

  • 1Breast Cancer Biology Group, Translational Research Department, Institut Curie-PSL Research University, 75005 Paris, France.

Cancers
|January 21, 2022
PubMed

Insights

Targeting protein arginine methyltransferase 1 (PRMT1) shows promise for triple-negative breast cancer (TNBC) therapy. Inhibiting PRMT1 induces DNA damage and apoptosis, and its combination with chemotherapy may improve TNBC treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to high relapse rates post-chemotherapy.
  • Identifying novel therapeutic targets is crucial for improving outcomes in TNBC patients.

Purpose of the Study:

  • To investigate the role of protein arginine methyltransferase 1 (PRMT1) in breast cancer, particularly TNBC.
  • To evaluate the therapeutic potential of targeting PRMT1 in TNBC models.

Main Methods:

  • Assessed PRMT1 expression across breast cancer subtypes.
  • Investigated the effects of PRMT1 depletion on cancer cell survival, DNA damage, and apoptosis.
  • Utilized transcriptomic analysis and chromatin immunoprecipitation to identify PRMT1-regulated pathways (EGFR, Wnt).
  • Evaluated the efficacy of PRMT1 inhibitors in TNBC cell lines and a xenograft model.
  • Assessed synergistic effects of PRMT1 inhibitors with standard chemotherapies and erlotinib.

Main Results:

  • PRMT1 is highly expressed in all breast cancer subtypes.
  • PRMT1 depletion induces DNA damage and apoptosis, decreasing cell survival.
  • PRMT1 regulates the epidermal growth factor receptor (EGFR) and Wnt signaling pathways.
  • PRMT1 enzymatic activity is essential for canonical Wnt pathway stimulation.
  • Type I PRMT inhibitors reduce breast cancer cell proliferation and exhibit anti-tumor activity in TNBC xenografts.
  • PRMT1 inhibitors show synergistic effects with certain TNBC chemotherapies and erlotinib.

Conclusions:

  • PRMT1 plays a significant role in breast cancer progression by regulating key signaling pathways.
  • Targeting PRMT1, particularly with Type I PRMT inhibitors, offers a potential therapeutic strategy for TNBC.
  • Combination therapy involving PRMT1 inhibitors, chemotherapy, and EGFR inhibitors may enhance treatment efficacy for TNBC patients.
Keywords:
EGFRPRMT1Wnt signalingbreast cancerdrug combinations

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