Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis

Colorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC-related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation of PU.1, a pioneer factor, which in turn bin...

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Autores: Wang, Lihua, Wang, Ergang, Prado Balcazar, Jorge, Wu, Zhenzhen, Xiang, Kun, Wang, Yi, Huang, Qiang, Negrete, Marcos, Chen, Kai‐yuan, Li, Wei, Fu, Yujie, Dohlman, Anders, Mines, Robert, Zhang, Liwen, Kobayashi, Yoshihiko, Chen, Tianyi, Shi, Guizhi, Shen, John Paul, Kopetz, Scott, Tata, Purushothama Rao, Moreno Aguado, Víctor, Gersbach, Charles, Crawford, Gregory, Hsu, David, Huang, Emina, Bu, Pengcheng, Shen, Xiling
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/179937
Acceso en línea:https://hdl.handle.net/2445/179937
Access Level:acceso abierto
Palabra clave:Càncer colorectal
Metàstasi
Colorectal cancer
Metastasis
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spelling Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 AxisWang, LihuaWang, ErgangPrado Balcazar, JorgeWu, ZhenzhenXiang, KunWang, YiHuang, QiangNegrete, MarcosChen, Kai‐yuanLi, WeiFu, YujieDohlman, AndersMines, RobertZhang, LiwenKobayashi, YoshihikoChen, TianyiShi, GuizhiShen, John PaulKopetz, ScottTata, Purushothama RaoMoreno Aguado, VíctorGersbach, CharlesCrawford, GregoryHsu, DavidHuang, EminaBu, PengchengShen, XilingCàncer colorectalMetàstasiColorectal cancerMetastasisColorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC-related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation of PU.1, a pioneer factor, which in turn binds and opens chromatin regions of downstream effector genes. PU.1 increases histone acetylation at the DPP4 locus. Precise epigenetic silencing by CRISPR/dCas9KRAB or CRISPR/dCas9HDAC revealed that individual PU.1-remodeled regulatory elements collectively modulate DPP4 expression and liver metastasis growth. Genetic silencing or pharmacological inhibition of each factor along this chromatin remodeling axis strongly suppressed liver metastasis. Therefore, microenvironment-induced epimutation is an important mechanism for metastatic tumor cells to grow in their new niche. This study presents a potential strategy to target chromatin remodeling in metastatic cancer and the promise of repurposing drugs to treat metastasis.Wiley2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/179937Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1002/advs.202004673Advanced Science, 2021, vol. 8, p. 2004673https://doi.org/10.1002/advs.202004673cc by (c) Wang, Lihua et al, 2021http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1799372026-05-27T06:46:51Z
dc.title.none.fl_str_mv Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis
title Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis
spellingShingle Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis
Wang, Lihua
Càncer colorectal
Metàstasi
Colorectal cancer
Metastasis
title_short Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis
title_full Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis
title_fullStr Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis
title_full_unstemmed Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis
title_sort Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis
dc.creator.none.fl_str_mv Wang, Lihua
Wang, Ergang
Prado Balcazar, Jorge
Wu, Zhenzhen
Xiang, Kun
Wang, Yi
Huang, Qiang
Negrete, Marcos
Chen, Kai‐yuan
Li, Wei
Fu, Yujie
Dohlman, Anders
Mines, Robert
Zhang, Liwen
Kobayashi, Yoshihiko
Chen, Tianyi
Shi, Guizhi
Shen, John Paul
Kopetz, Scott
Tata, Purushothama Rao
Moreno Aguado, Víctor
Gersbach, Charles
Crawford, Gregory
Hsu, David
Huang, Emina
Bu, Pengcheng
Shen, Xiling
author Wang, Lihua
author_facet Wang, Lihua
Wang, Ergang
Prado Balcazar, Jorge
Wu, Zhenzhen
Xiang, Kun
Wang, Yi
Huang, Qiang
Negrete, Marcos
Chen, Kai‐yuan
Li, Wei
Fu, Yujie
Dohlman, Anders
Mines, Robert
Zhang, Liwen
Kobayashi, Yoshihiko
Chen, Tianyi
Shi, Guizhi
Shen, John Paul
Kopetz, Scott
Tata, Purushothama Rao
Moreno Aguado, Víctor
Gersbach, Charles
Crawford, Gregory
Hsu, David
Huang, Emina
Bu, Pengcheng
Shen, Xiling
author_role author
author2 Wang, Ergang
Prado Balcazar, Jorge
Wu, Zhenzhen
Xiang, Kun
Wang, Yi
Huang, Qiang
Negrete, Marcos
Chen, Kai‐yuan
Li, Wei
Fu, Yujie
Dohlman, Anders
Mines, Robert
Zhang, Liwen
Kobayashi, Yoshihiko
Chen, Tianyi
Shi, Guizhi
Shen, John Paul
Kopetz, Scott
Tata, Purushothama Rao
Moreno Aguado, Víctor
Gersbach, Charles
Crawford, Gregory
Hsu, David
Huang, Emina
Bu, Pengcheng
Shen, Xiling
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer colorectal
Metàstasi
Colorectal cancer
Metastasis
topic Càncer colorectal
Metàstasi
Colorectal cancer
Metastasis
description Colorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC-related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation of PU.1, a pioneer factor, which in turn binds and opens chromatin regions of downstream effector genes. PU.1 increases histone acetylation at the DPP4 locus. Precise epigenetic silencing by CRISPR/dCas9KRAB or CRISPR/dCas9HDAC revealed that individual PU.1-remodeled regulatory elements collectively modulate DPP4 expression and liver metastasis growth. Genetic silencing or pharmacological inhibition of each factor along this chromatin remodeling axis strongly suppressed liver metastasis. Therefore, microenvironment-induced epimutation is an important mechanism for metastatic tumor cells to grow in their new niche. This study presents a potential strategy to target chromatin remodeling in metastatic cancer and the promise of repurposing drugs to treat metastasis.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/179937
url https://hdl.handle.net/2445/179937
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1002/advs.202004673
Advanced Science, 2021, vol. 8, p. 2004673
https://doi.org/10.1002/advs.202004673
dc.rights.none.fl_str_mv cc by (c) Wang, Lihua et al, 2021
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Wang, Lihua et al, 2021
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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