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...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2019-08-01
|
Series: | Cancer Medicine |
Subjects: | |
Online Access: | https://doi.org/10.1002/cam4.2349 |
id |
doaj-22764bbdcb364bc4b404c85a7df3b4b9 |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT jinpeng recql5playsanessentialroleinmaintaininggenomestabilityandviabilityoftriplenegativebreastcancercells AT lichuntang recql5playsanessentialroleinmaintaininggenomestabilityandviabilityoftriplenegativebreastcancercells AT mengjiaocai recql5playsanessentialroleinmaintaininggenomestabilityandviabilityoftriplenegativebreastcancercells AT huanchen recql5playsanessentialroleinmaintaininggenomestabilityandviabilityoftriplenegativebreastcancercells AT jieminwong recql5playsanessentialroleinmaintaininggenomestabilityandviabilityoftriplenegativebreastcancercells AT puminzhang recql5playsanessentialroleinmaintaininggenomestabilityandviabilityoftriplenegativebreastcancercells |
_version_ |
1725222939183284224 |