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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| Format: | Article |
| Publication date: | 2017 |
| Country: | España |
| Institution: | Universitat Autònoma de Barcelona |
| Repository: | Dipòsit Digital de Documents de la UAB |
| Language: | English |
| OAI Identifier: | oai:ddd.uab.cat:186380 |
| Online Access: | https://ddd.uab.cat/record/186380 https://dx.doi.org/urn:doi:10.18632/oncotarget.20698 |
| Access Level: | Open access |
| Keyword: | MicroRNAs MiR-200 Epithelial reprogramming Progenitor luminal cells Invasive ductal breast cancer |
| _version_ | 1878741634689007616 |
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| author | Sánchez-Cid, Lourdes |
| 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 |
| author_browse | Alonso, Immaculada Arguimbau, Judit Bermudo, Raquel Blanco Fernández, Jerónimo Caparrós, Xavier Cascante, Marta Fernández, Pedro Luis|||0000-0002-8618-4597 Fueyo Arévalo, Raquel Guerra-Rebollo, Marta Kang, Yibin Lozano, Juan José Martínez-Balbás, Marian Muñoz, Montserrat Paris-Coderch, Laia Pons, Mònica Rafii, Arash Rubio, Nuria Segura, Miquel F. Soriano, Aroa|||0000-0001-9659-1471 Sánchez-Cid, Lourdes Thomson, Timothy M. Weiss, Stephen J. Zodda, Erika |
| 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 |
| collection | Dipòsit Digital de Documents de la UAB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_e8a7ccded29a2a71cff78a2390b577e0 |
| institution | Universitat Autònoma de Barcelona |
| instname_str | Universitat Autònoma de Barcelona |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:ddd.uab.cat:186380 |
| publishDate | 2017 |
| publishDateSort | 2017 |
| reponame_str | Dipòsit Digital de Documents de la UAB |
| spelling | MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells 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. MicroRNAs MiR-200 Epithelial reprogramming Progenitor luminal cells Invasive ductal breast cancer 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. https://ddd.uab.cat/record/186380 https://dx.doi.org/urn:doi:10.18632/oncotarget.20698 |
| 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 | 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_short | 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 |
| topic | MicroRNAs MiR-200 Epithelial reprogramming Progenitor luminal cells Invasive ductal breast cancer |
| topic_facet | MicroRNAs MiR-200 Epithelial reprogramming Progenitor luminal cells Invasive ductal breast cancer |
| url | https://ddd.uab.cat/record/186380 https://dx.doi.org/urn:doi:10.18632/oncotarget.20698 |