MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells

MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant...

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Autores: Sánchez-Cid, Lourdes, Pons, Mònica, Lozano, Juan José, Rubio, Nuria, Guerra-Rebollo, Marta, Soriano, Aroa|||0000-0001-9659-1471, Paris-Coderch, Laia, Segura, Miquel F., Fueyo Arévalo, Raquel, Arguimbau, Judit, Zodda, Erika, Bermudo, Raquel, Alonso, Immaculada, Caparrós, Xavier, Cascante, Marta, Rafii, Arash, Kang, Yibin, Martínez-Balbás, Marian, Weiss, Stephen J., Blanco Fernández, Jerónimo, Muñoz, Montserrat, Fernández, Pedro Luis|||0000-0002-8618-4597, Thomson, Timothy M.
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:186380
Acceso en línea:https://ddd.uab.cat/record/186380
https://dx.doi.org/urn:doi:10.18632/oncotarget.20698
Access Level:acceso abierto
Palabra clave:MicroRNAs
MiR-200
Epithelial reprogramming
Progenitor luminal cells
Invasive ductal breast cancer
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spelling MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cellsSánchez-Cid, LourdesPons, MònicaLozano, Juan JoséRubio, NuriaGuerra-Rebollo, MartaSoriano, Aroa|||0000-0001-9659-1471Paris-Coderch, LaiaSegura, Miquel F.Fueyo Arévalo, RaquelArguimbau, JuditZodda, ErikaBermudo, RaquelAlonso, ImmaculadaCaparrós, XavierCascante, MartaRafii, ArashKang, YibinMartínez-Balbás, MarianWeiss, Stephen J.Blanco Fernández, JerónimoMuñoz, MontserratFernández, Pedro Luis|||0000-0002-8618-4597Thomson, Timothy M.MicroRNAsMiR-200Epithelial reprogrammingProgenitor luminal cellsInvasive ductal breast cancerMicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo. MiR-200s also induced the constitutive activation of the PI3K-Akt signaling through downregulation of PTEN, and the enhanced mammosphere growth and ALDH activity induced in MCF10CA1h cells by miR-200s required the activation of this signaling pathway. Interestingly, the morphology of tumors formed in vivo by cells expressing miR-200s was reminiscent of metaplastic breast cancer (MBC). Indeed, the epithelial components of MBC samples expressed significantly higher levels of miR-200s than their mesenchymal components and displayed a marker profile compatible with luminal progenitor cells. We propose that microRNAs of the miR-200 family promote traits of highly proliferative breast luminal progenitor cells, thereby exacerbating the growth and metastatic properties of transformed mammary epithelial cells.Universitat Autònoma de Barcelona 22017-01-0120172017-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/186380https://dx.doi.org/urn:doi:10.18632/oncotarget.20698reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia e Innovación https://doi.org/10.13039/501100004837 FIS/PI080274Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2012-40017-C02-02Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12-0036-0036Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 SAF2011/24686Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2012/40017-C02-01Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015/66984-C2-1-RAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2009/SGR-1482Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12-0037-0016Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-660Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD09-0076-0038open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/3.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1863802026-06-06T12:50:31Z
dc.title.none.fl_str_mv MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells
title MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells
spellingShingle MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells
Sánchez-Cid, Lourdes
MicroRNAs
MiR-200
Epithelial reprogramming
Progenitor luminal cells
Invasive ductal breast cancer
title_short MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells
title_full MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells
title_fullStr MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells
title_full_unstemmed MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells
title_sort MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells
dc.creator.none.fl_str_mv Sánchez-Cid, Lourdes
Pons, Mònica
Lozano, Juan José
Rubio, Nuria
Guerra-Rebollo, Marta
Soriano, Aroa|||0000-0001-9659-1471
Paris-Coderch, Laia
Segura, Miquel F.
Fueyo Arévalo, Raquel
Arguimbau, Judit
Zodda, Erika
Bermudo, Raquel
Alonso, Immaculada
Caparrós, Xavier
Cascante, Marta
Rafii, Arash
Kang, Yibin
Martínez-Balbás, Marian
Weiss, Stephen J.
Blanco Fernández, Jerónimo
Muñoz, Montserrat
Fernández, Pedro Luis|||0000-0002-8618-4597
Thomson, Timothy M.
author Sánchez-Cid, Lourdes
author_facet Sánchez-Cid, Lourdes
Pons, Mònica
Lozano, Juan José
Rubio, Nuria
Guerra-Rebollo, Marta
Soriano, Aroa|||0000-0001-9659-1471
Paris-Coderch, Laia
Segura, Miquel F.
Fueyo Arévalo, Raquel
Arguimbau, Judit
Zodda, Erika
Bermudo, Raquel
Alonso, Immaculada
Caparrós, Xavier
Cascante, Marta
Rafii, Arash
Kang, Yibin
Martínez-Balbás, Marian
Weiss, Stephen J.
Blanco Fernández, Jerónimo
Muñoz, Montserrat
Fernández, Pedro Luis|||0000-0002-8618-4597
Thomson, Timothy M.
author_role author
author2 Pons, Mònica
Lozano, Juan José
Rubio, Nuria
Guerra-Rebollo, Marta
Soriano, Aroa|||0000-0001-9659-1471
Paris-Coderch, Laia
Segura, Miquel F.
Fueyo Arévalo, Raquel
Arguimbau, Judit
Zodda, Erika
Bermudo, Raquel
Alonso, Immaculada
Caparrós, Xavier
Cascante, Marta
Rafii, Arash
Kang, Yibin
Martínez-Balbás, Marian
Weiss, Stephen J.
Blanco Fernández, Jerónimo
Muñoz, Montserrat
Fernández, Pedro Luis|||0000-0002-8618-4597
Thomson, Timothy M.
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.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv MicroRNAs
MiR-200
Epithelial reprogramming
Progenitor luminal cells
Invasive ductal breast cancer
topic MicroRNAs
MiR-200
Epithelial reprogramming
Progenitor luminal cells
Invasive ductal breast cancer
description MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo. MiR-200s also induced the constitutive activation of the PI3K-Akt signaling through downregulation of PTEN, and the enhanced mammosphere growth and ALDH activity induced in MCF10CA1h cells by miR-200s required the activation of this signaling pathway. Interestingly, the morphology of tumors formed in vivo by cells expressing miR-200s was reminiscent of metaplastic breast cancer (MBC). Indeed, the epithelial components of MBC samples expressed significantly higher levels of miR-200s than their mesenchymal components and displayed a marker profile compatible with luminal progenitor cells. We propose that microRNAs of the miR-200 family promote traits of highly proliferative breast luminal progenitor cells, thereby exacerbating the growth and metastatic properties of transformed mammary epithelial cells.
publishDate 2017
dc.date.none.fl_str_mv 2
2017-01-01
2017
2017-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/186380
https://dx.doi.org/urn:doi:10.18632/oncotarget.20698
url https://ddd.uab.cat/record/186380
https://dx.doi.org/urn:doi:10.18632/oncotarget.20698
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 FIS/PI080274
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2012-40017-C02-02
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12-0036-0036
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 SAF2011/24686
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2012/40017-C02-01
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015/66984-C2-1-R
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2009/SGR-1482
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12-0037-0016
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-660
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD09-0076-0038
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/3.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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