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Fluorescence-Based Detection of FEN1 Nuclease Activity and Screening of Small-Molecule Inhibitors
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Fluorescence-Based Detection of FEN1 Nuclease Activity and Screening of Small-Molecule Inhibitors

Published on: June 27, 2025

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Targeting DNA Flap Endonuclease 1 to Impede Breast Cancer Progression

Lingfeng He1, Yilan Zhang1, Hongfang Sun1

  • 1Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210023, China.

Ebiomedicine
|November 18, 2016
PubMed

Insights

DNA flap endonuclease 1 (FEN1) is overexpressed in breast cancer and crucial for cancer cell proliferation. Inhibiting FEN1 with compound SC13 shows promise for cancer therapy by disrupting DNA repair and sensitizing cells to treatment.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • DNA flap endonuclease 1 (FEN1) is vital for maintaining genome stability through DNA replication and repair.
  • FEN1 suppression leads to DNA replication defects, DNA double-strand breaks, and apoptosis.
  • FEN1's role suggests its potential as a therapeutic target in cancer treatment.

Purpose of the Study:

  • To investigate the role of FEN1 in breast cancer proliferation and its potential as a therapeutic target.
  • To identify and evaluate a small molecule inhibitor of FEN1 activity.

Main Methods:

  • Assessed FEN1 expression in breast cancer tissues.
  • Manipulated FEN1 levels in cancer cells to study its effects on proliferation and drug response.
  • Identified and characterized the FEN1 inhibitor SC13 in vitro and in cell models.
  • Evaluated SC13's efficacy in a mouse model of cancer progression.

Main Results:

  • FEN1 is overexpressed in breast cancers and essential for rapid cancer cell proliferation.
  • FEN1 inhibition alters cancer cell sensitivity to chemotherapeutic drugs.
  • The small molecule SC13 specifically inhibits FEN1, suppressing cancer cell proliferation and inducing cytotoxicity.
  • SC13 sensitizes cancer cells to DNA damage-inducing therapies and impedes tumor progression in vivo.

Conclusions:

  • FEN1 is a critical target for breast cancer therapy due to its role in proliferation and DNA repair.
  • The FEN1 inhibitor SC13 demonstrates significant potential for treating breast cancer and potentially other cancers.
  • Targeting FEN1 offers a novel therapeutic strategy to enhance the effectiveness of existing cancer treatments.
Keywords:
Breast cancerChemotherapeutic drugDNA replication and repairFlap endonuclease 1 (FEN1)Small molecular inhibitor

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