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

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...

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Main Authors: Jin Peng, Lichun Tang, Mengjiao Cai, Huan Chen, Jiemin Wong, Pumin Zhang
Format: Article
Language:English
Published: Wiley 2019-08-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.2349
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spelling doaj-22764bbdcb364bc4b404c85a7df3b4b92020-11-25T00:57:40ZengWileyCancer Medicine2045-76342019-08-018104743475210.1002/cam4.2349RECQL5 plays an essential role in maintaining genome stability and viability of triple‐negative breast cancer cellsJin Peng0Lichun Tang1Mengjiao Cai2Huan Chen3Jiemin Wong4Pumin Zhang5Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences East China Normal University Shanghai ChinaState Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center Beijing Institute of Lifeomics Beijing ChinaDepartment of Oncology, The First Affiliated Hospital Xi'an Jiaotong University Medical College Xi'an ChinaState Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center Beijing Institute of Lifeomics Beijing ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences East China Normal University Shanghai ChinaState Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center Beijing Institute of Lifeomics Beijing ChinaAbstract 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.https://doi.org/10.1002/cam4.2349DNA damageessential genegenomic stabilityRECQL5triple‐negative breast cancer
collection DOAJ
language English
format Article
sources DOAJ
author Jin Peng
Lichun Tang
Mengjiao Cai
Huan Chen
Jiemin Wong
Pumin Zhang
spellingShingle Jin Peng
Lichun Tang
Mengjiao Cai
Huan Chen
Jiemin Wong
Pumin Zhang
RECQL5 plays an essential role in maintaining genome stability and viability of triple‐negative breast cancer cells
Cancer Medicine
DNA damage
essential gene
genomic stability
RECQL5
triple‐negative breast cancer
author_facet Jin Peng
Lichun Tang
Mengjiao Cai
Huan Chen
Jiemin Wong
Pumin Zhang
author_sort Jin Peng
title RECQL5 plays an essential role in maintaining genome stability and viability of triple‐negative breast cancer cells
title_short RECQL5 plays an essential role in maintaining genome stability and viability of triple‐negative breast cancer cells
title_full RECQL5 plays an essential role in maintaining genome stability and viability of triple‐negative breast cancer cells
title_fullStr RECQL5 plays an essential role in maintaining genome stability and viability of triple‐negative breast cancer cells
title_full_unstemmed RECQL5 plays an essential role in maintaining genome stability and viability of triple‐negative breast cancer cells
title_sort recql5 plays an essential role in maintaining genome stability and viability of triple‐negative breast cancer cells
publisher Wiley
series Cancer Medicine
issn 2045-7634
publishDate 2019-08-01
description 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.
topic DNA damage
essential gene
genomic stability
RECQL5
triple‐negative breast cancer
url https://doi.org/10.1002/cam4.2349
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