Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineages

It is widely assumed that all normal somatic cells can equally perform homologous recombination (HR) and non-homologous end joining in the DNA damage response (DDR). Here, we show that the DDR in normal mammary gland inherently depends on the epithelial cell lineage identity. Bioinformatics, post-ir...

Descripción completa

Detalles Bibliográficos
Autores: Kim, Hyeyeon, Aliar, Kazeera, Tharmapalan, Pirashaanthy, Mccloskey, Curtis W., Kuttanamkuzhi, Abhijith, Grünwald, Barbara T., Palomero, Luis, Mahendralingam, Mathepan J., Waas, Matthew, Mer, Arvind S., Elliott, Mitchell J., Zhang, Bowen, Al-Zahrani, Khalid N., Langille, Ellen R., Parsons, Michael, Narala, Swami, Hofer, Stefan, Waterhouse, Paul D., Hakem, Razq, Haibe-Kains, Benjamin, Kislinger, Thomas, Schramek, Daniel, Cescon, David W., Pujana Genestar, M. Ángel, Berman, Hal K., Khokha, Rama
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/204202
Acceso en línea:https://hdl.handle.net/2445/204202
Access Level:acceso abierto
Palabra clave:Càncer de mama
Inhibidors enzimàtics
Breast cancer
Enzyme inhibitors
id ES_514cd0fe8c512871b3dd93d2b13a67db
oai_identifier_str oai:recercat.cat:2445/204202
network_acronym_str ES
network_name_str España
repository_id_str
spelling Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineagesKim, HyeyeonAliar, KazeeraTharmapalan, PirashaanthyMccloskey, Curtis W.Kuttanamkuzhi, AbhijithGrünwald, Barbara T.Palomero, LuisMahendralingam, Mathepan J.Waas, MatthewMer, Arvind S.Elliott, Mitchell J.Zhang, BowenAl-Zahrani, Khalid N.Langille, Ellen R.Parsons, MichaelNarala, SwamiHofer, StefanWaterhouse, Paul D.Hakem, RazqHaibe-Kains, BenjaminKislinger, ThomasSchramek, DanielCescon, David W.Pujana Genestar, M. ÁngelBerman, Hal K.Khokha, RamaCàncer de mamaInhibidors enzimàticsBreast cancerEnzyme inhibitorsIt is widely assumed that all normal somatic cells can equally perform homologous recombination (HR) and non-homologous end joining in the DNA damage response (DDR). Here, we show that the DDR in normal mammary gland inherently depends on the epithelial cell lineage identity. Bioinformatics, post-irradiation DNA damage repair kinetics, and clonogenic assays demonstrated luminal lineage exhibiting a more pronounced DDR and HR repair compared to the basal lineage. Consequently, basal progenitors were far more sensitive to poly(ADP-ribose) polymerase inhibitors (PARPis) in both mouse and human mammary epithelium. Furthermore, PARPi sensitivity of murine and human breast cancer cell lines as well as patient derived xenografts correlated with their molecular resemblance to the mammary progenitor lineages. Thus, mammary epithelial cells are intrinsically divergent in their DNA damage repair capacity and PARPi vulnerability, potentially influencing the clinical utility of this targeted therapy.Elsevier BV2023202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion27 p.application/pdfhttps://hdl.handle.net/2445/204202Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.celrep.2023.113256Cell Reports, 2023, vol. 42, num. 10https://doi.org/10.1016/j.celrep.2023.113256cc by-nc-nd (c) Kim, Hyeyeon et al., 2023http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2042022026-05-29T05:05:01Z
dc.title.none.fl_str_mv Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineages
title Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineages
spellingShingle Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineages
Kim, Hyeyeon
Càncer de mama
Inhibidors enzimàtics
Breast cancer
Enzyme inhibitors
title_short Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineages
title_full Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineages
title_fullStr Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineages
title_full_unstemmed Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineages
title_sort Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineages
dc.creator.none.fl_str_mv Kim, Hyeyeon
Aliar, Kazeera
Tharmapalan, Pirashaanthy
Mccloskey, Curtis W.
Kuttanamkuzhi, Abhijith
Grünwald, Barbara T.
Palomero, Luis
Mahendralingam, Mathepan J.
Waas, Matthew
Mer, Arvind S.
Elliott, Mitchell J.
Zhang, Bowen
Al-Zahrani, Khalid N.
Langille, Ellen R.
Parsons, Michael
Narala, Swami
Hofer, Stefan
Waterhouse, Paul D.
Hakem, Razq
Haibe-Kains, Benjamin
Kislinger, Thomas
Schramek, Daniel
Cescon, David W.
Pujana Genestar, M. Ángel
Berman, Hal K.
Khokha, Rama
author Kim, Hyeyeon
author_facet Kim, Hyeyeon
Aliar, Kazeera
Tharmapalan, Pirashaanthy
Mccloskey, Curtis W.
Kuttanamkuzhi, Abhijith
Grünwald, Barbara T.
Palomero, Luis
Mahendralingam, Mathepan J.
Waas, Matthew
Mer, Arvind S.
Elliott, Mitchell J.
Zhang, Bowen
Al-Zahrani, Khalid N.
Langille, Ellen R.
Parsons, Michael
Narala, Swami
Hofer, Stefan
Waterhouse, Paul D.
Hakem, Razq
Haibe-Kains, Benjamin
Kislinger, Thomas
Schramek, Daniel
Cescon, David W.
Pujana Genestar, M. Ángel
Berman, Hal K.
Khokha, Rama
author_role author
author2 Aliar, Kazeera
Tharmapalan, Pirashaanthy
Mccloskey, Curtis W.
Kuttanamkuzhi, Abhijith
Grünwald, Barbara T.
Palomero, Luis
Mahendralingam, Mathepan J.
Waas, Matthew
Mer, Arvind S.
Elliott, Mitchell J.
Zhang, Bowen
Al-Zahrani, Khalid N.
Langille, Ellen R.
Parsons, Michael
Narala, Swami
Hofer, Stefan
Waterhouse, Paul D.
Hakem, Razq
Haibe-Kains, Benjamin
Kislinger, Thomas
Schramek, Daniel
Cescon, David W.
Pujana Genestar, M. Ángel
Berman, Hal K.
Khokha, Rama
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
dc.subject.none.fl_str_mv Càncer de mama
Inhibidors enzimàtics
Breast cancer
Enzyme inhibitors
topic Càncer de mama
Inhibidors enzimàtics
Breast cancer
Enzyme inhibitors
description It is widely assumed that all normal somatic cells can equally perform homologous recombination (HR) and non-homologous end joining in the DNA damage response (DDR). Here, we show that the DDR in normal mammary gland inherently depends on the epithelial cell lineage identity. Bioinformatics, post-irradiation DNA damage repair kinetics, and clonogenic assays demonstrated luminal lineage exhibiting a more pronounced DDR and HR repair compared to the basal lineage. Consequently, basal progenitors were far more sensitive to poly(ADP-ribose) polymerase inhibitors (PARPis) in both mouse and human mammary epithelium. Furthermore, PARPi sensitivity of murine and human breast cancer cell lines as well as patient derived xenografts correlated with their molecular resemblance to the mammary progenitor lineages. Thus, mammary epithelial cells are intrinsically divergent in their DNA damage repair capacity and PARPi vulnerability, potentially influencing the clinical utility of this targeted therapy.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
2023
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/2445/204202
url https://hdl.handle.net/2445/204202
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/10.1016/j.celrep.2023.113256
Cell Reports, 2023, vol. 42, num. 10
https://doi.org/10.1016/j.celrep.2023.113256
dc.rights.none.fl_str_mv cc by-nc-nd (c) Kim, Hyeyeon et al., 2023
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Kim, Hyeyeon et al., 2023
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 27 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869407947675664384
score 15,811543

Similares en LA Referencia