CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis because of its high propensity to metastasize and its immunosuppressive microenvironment. Using a panel of pancreatic cancer cell lines, three-dimensional (3D) invasion systems, microarray gene signatures, microfluidic devices, mouse...

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Autores: Samain, Remi, Maiques, Oscar, Monger, Joanne, Lam, Hoyin, Candido, Juliana, George, Samantha, Ferrari, Nicola, Kohihammer, Leonie, Lunetto, Sophia, Varela, Adrian, Orgaz, Jose L., Vilardell, Felip, Olsina, Jorge Juan, Matias-Guiu, Xavier, 1958-, Sarker, Debashis, Biddle, Adrian, Balkwill, Frances R., Eyles, Jim, Wilkinson, Robert W., Kocher, Hemant M., Calvo, Fernando, Wells, Claire M., Sanz Moreno, Victoria
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:2445/208708
Acceso en línea:https://hdl.handle.net/2445/208708
Access Level:acceso abierto
Palabra clave:Amebes
Proteïnes citosquelètiques
Amoeba
Cytoskeletal Proteins
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spelling CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cellsSamain, RemiMaiques, OscarMonger, JoanneLam, HoyinCandido, JulianaGeorge, SamanthaFerrari, NicolaKohihammer, LeonieLunetto, SophiaVarela, AdrianOrgaz, Jose L.Vilardell, FelipOlsina, Jorge JuanMatias-Guiu, Xavier, 1958-Sarker, DebashisBiddle, AdrianBalkwill, Frances R.Eyles, JimWilkinson, Robert W.Kocher, Hemant M.Calvo, FernandoWells, Claire M.Sanz Moreno, VictoriaAmebesProteïnes citosquelètiquesAmoebaCytoskeletal ProteinsPancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis because of its high propensity to metastasize and its immunosuppressive microenvironment. Using a panel of pancreatic cancer cell lines, three-dimensional (3D) invasion systems, microarray gene signatures, microfluidic devices, mouse models, and intravital imaging, we demonstrate that ROCK-Myosin II activity in PDAC cells supports a transcriptional program conferring amoeboid invasive and immunosuppressive traits and in vivo metastatic abilities. Moreover, we find that immune checkpoint CD73 is highly expressed in amoeboid PDAC cells and drives their invasive, metastatic, and immunomodulatory traits. Mechanistically, CD73 activates RhoA-ROCK-Myosin II downstream of PI3K. Tissue microarrays of human PDAC biopsies combined with bioinformatic analysis reveal that rounded-amoeboid invasive cells with high CD73-ROCK-Myosin II activity and their immunosuppressive microenvironment confer poor prognosis to patients. We propose targeting amoeboid PDAC cells as a therapeutic strategy.American Association for the Advancement of Science (AAAS)2024202420232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion20 p.application/pdfhttps://hdl.handle.net/2445/208708Articles 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/10.1126/sciadv.adi0244Science Advances, 2023, vol. 9, num. 42https://doi.org/10.1126/sciadv.adi0244cc by (c) Samain, Remi et al., 2023http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2087082026-05-29T05:05:01Z
dc.title.none.fl_str_mv CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells
title CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells
spellingShingle CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells
Samain, Remi
Amebes
Proteïnes citosquelètiques
Amoeba
Cytoskeletal Proteins
title_short CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells
title_full CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells
title_fullStr CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells
title_full_unstemmed CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells
title_sort CD73 controls Myosin II–driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells
dc.creator.none.fl_str_mv Samain, Remi
Maiques, Oscar
Monger, Joanne
Lam, Hoyin
Candido, Juliana
George, Samantha
Ferrari, Nicola
Kohihammer, Leonie
Lunetto, Sophia
Varela, Adrian
Orgaz, Jose L.
Vilardell, Felip
Olsina, Jorge Juan
Matias-Guiu, Xavier, 1958-
Sarker, Debashis
Biddle, Adrian
Balkwill, Frances R.
Eyles, Jim
Wilkinson, Robert W.
Kocher, Hemant M.
Calvo, Fernando
Wells, Claire M.
Sanz Moreno, Victoria
author Samain, Remi
author_facet Samain, Remi
Maiques, Oscar
Monger, Joanne
Lam, Hoyin
Candido, Juliana
George, Samantha
Ferrari, Nicola
Kohihammer, Leonie
Lunetto, Sophia
Varela, Adrian
Orgaz, Jose L.
Vilardell, Felip
Olsina, Jorge Juan
Matias-Guiu, Xavier, 1958-
Sarker, Debashis
Biddle, Adrian
Balkwill, Frances R.
Eyles, Jim
Wilkinson, Robert W.
Kocher, Hemant M.
Calvo, Fernando
Wells, Claire M.
Sanz Moreno, Victoria
author_role author
author2 Maiques, Oscar
Monger, Joanne
Lam, Hoyin
Candido, Juliana
George, Samantha
Ferrari, Nicola
Kohihammer, Leonie
Lunetto, Sophia
Varela, Adrian
Orgaz, Jose L.
Vilardell, Felip
Olsina, Jorge Juan
Matias-Guiu, Xavier, 1958-
Sarker, Debashis
Biddle, Adrian
Balkwill, Frances R.
Eyles, Jim
Wilkinson, Robert W.
Kocher, Hemant M.
Calvo, Fernando
Wells, Claire M.
Sanz Moreno, Victoria
author2_role 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 Amebes
Proteïnes citosquelètiques
Amoeba
Cytoskeletal Proteins
topic Amebes
Proteïnes citosquelètiques
Amoeba
Cytoskeletal Proteins
description Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis because of its high propensity to metastasize and its immunosuppressive microenvironment. Using a panel of pancreatic cancer cell lines, three-dimensional (3D) invasion systems, microarray gene signatures, microfluidic devices, mouse models, and intravital imaging, we demonstrate that ROCK-Myosin II activity in PDAC cells supports a transcriptional program conferring amoeboid invasive and immunosuppressive traits and in vivo metastatic abilities. Moreover, we find that immune checkpoint CD73 is highly expressed in amoeboid PDAC cells and drives their invasive, metastatic, and immunomodulatory traits. Mechanistically, CD73 activates RhoA-ROCK-Myosin II downstream of PI3K. Tissue microarrays of human PDAC biopsies combined with bioinformatic analysis reveal that rounded-amoeboid invasive cells with high CD73-ROCK-Myosin II activity and their immunosuppressive microenvironment confer poor prognosis to patients. We propose targeting amoeboid PDAC cells as a therapeutic strategy.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2024
2024
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/2445/208708
url https://hdl.handle.net/2445/208708
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/10.1126/sciadv.adi0244
Science Advances, 2023, vol. 9, num. 42
https://doi.org/10.1126/sciadv.adi0244
dc.rights.none.fl_str_mv cc by (c) Samain, Remi et al., 2023
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Samain, Remi et al., 2023
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 20 p.
application/pdf
dc.publisher.none.fl_str_mv American Association for the Advancement of Science (AAAS)
publisher.none.fl_str_mv American Association for the Advancement of Science (AAAS)
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_ 1869419380384727040
score 15,811543

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