RECQL5 plays an essential role in maintaining genome stability and viability of triple-negative breast cancer cells

Cancer Med. 2019 Aug;8(10):4743-4752. doi: 10.1002/cam4.2349. Epub 2019 Jun 23.

Abstract

Triple-negative breast cancer (TNBC) is a malignancy that currently lacks targeted therapies. The majority of TNBCs can be characterized as basal-like and has an expression profile enriched with genes involved in DNA damage repair and checkpoint response. Here, we report that TNBC cells are under replication stress and are constantly generating DNA double-strand breaks, which is not seen in non-TNBC cells. Consequently, we found that RECQL5, which encodes a RecQ family DNA helicase involved in many aspects of DNA metabolism including replication and repair, was essential for TNBC cells to survive and proliferate in vitro and in vivo. Compromising RECQL5 function in TNBC cells results in persistence of DNA damage, G2 arrest, and ultimately, cessation of proliferation. Our results suggest RECQL5 may be a potential therapeutic target for TNBC.

Keywords: DNA damage; RECQL5; essential gene; genomic stability; triple-negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • DNA Replication
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genomic Instability*
  • Humans
  • Neoplasm Transplantation
  • RecQ Helicases / genetics*
  • RecQ Helicases / metabolism*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology*

Substances

  • RECQL5 protein, human
  • RecQ Helicases