Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition
Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer model...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Fecha de publicación: | 2017 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:291146 |
| Acesso em linha: | https://ddd.uab.cat/record/291146 https://dx.doi.org/urn:doi:10.1038/onc.2016.427 |
| Access Level: | acceso abierto |
| Palavra-chave: | Adaptor Proteins, Signal Transducing Adult Aged Breast Neoplasms Carrier Proteins Cell Proliferation DNA-Binding Proteins Female Gene Expression Regulation, Neoplastic Humans Lung Neoplasms MCF-7 Cells Microfilament Proteins Middle Aged Neoplasm Metastasis Osteonectin Proto-Oncogenes Signal Transduction SOX9 Transcription Factor TOR Serine-Threonine Kinases Transcription Factors Xenograft Model Antitumor Assays |
| id |
ES_a0476dee3ea9bae0eebb77462901fc9e |
|---|---|
| oai_identifier_str |
oai:ddd.uab.cat:291146 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| dc.title.none.fl_str_mv |
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition |
| title |
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition |
| spellingShingle |
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition Mateo, Francesca|||0000-0002-2342-7010 Adaptor Proteins, Signal Transducing Adult Aged Breast Neoplasms Carrier Proteins Cell Proliferation DNA-Binding Proteins Female Gene Expression Regulation, Neoplastic Humans Lung Neoplasms MCF-7 Cells Microfilament Proteins Middle Aged Neoplasm Metastasis Osteonectin Proto-Oncogenes Signal Transduction SOX9 Transcription Factor TOR Serine-Threonine Kinases Transcription Factors Xenograft Model Antitumor Assays |
| title_short |
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition |
| title_full |
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition |
| title_fullStr |
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition |
| title_full_unstemmed |
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition |
| title_sort |
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition |
| dc.creator.none.fl_str_mv |
Mateo, Francesca|||0000-0002-2342-7010 Arenas, Enrique J.|||0000-0001-7076-2666 Aguilar, Helena Serra-Musach, Jordi Ruiz de Garibay, Gorka|||0000-0001-9936-8419 Boni, Jacopo|||0000-0003-2626-9393 Maicas, Miren|||0000-0003-1404-5552 Du, Shisuo Iorio, Francesco|||0000-0001-7063-8913 Herranz-Ors, Carmen|||0000-0002-2866-0321 Islam, Abul Prado, X. Llorente, Alicia Petit Montserrat, Anna|||0000-0002-9284-095X Vidal, August|||0000-0001-5727-2099 Català, Isabel Soler, Teresa Venturas, G. Rojo-Sebastian, Alejandro|||0000-0001-6439-3518 Serra, Helena Cuadras, Daniel|||0000-0001-8780-1764 Blanco Guillermo, Ignacio|||0000-0002-7414-7481 Lozano, José Canals, Francesc|||0000-0002-0650-1135 Sieuwerts, Anieta M. De Weerd, Vanja Look, Maxime P. Puertas, Sara García, Nadia Perkins, Archibald S. Bonifaci, Núria|||0000-0002-8193-6825 Skowron, Margaretha A. Gómez-Baldó, Laia Hernández, Vanessa Martínez-Aranda, Antonio Martínez-Iniesta, Maria|||0000-0001-6252-6671 Serrat Farran, Xènia|||0000-0001-7611-5400 Cerón, Julián|||0000-0003-4739-2243 Brunet, Joan|||0000-0003-1945-3512 Barretina-Ginesta, Maria-Pilar|||0000-0003-0074-6614 Gil, Mercedes|||0000-0002-7387-2139 Falo, Catalina|||0000-0002-5714-6823 Fernández, Adela Morilla, Idoia Pernas, Sonia|||0000-0002-1485-5080 Plà, Maria Jesus Andreu, Xavier Seguí Palmer, Miguel Ángel|||0000-0002-5103-6746 Ballester, Rosa|||0000-0002-7870-4185 Castellà Fernández, Eva Nellist, Mark D. Morales, Saleta Valls, Joan|||0000-0002-4806-7568 Velasco Sánchez, Ana Matías-Guiu, Xavier|||0000-0002-7201-6605 Figueras, Agnes Sánchez-Mut, José Vicente|||0000-0002-9292-8521 Sánchez Céspedes, Montse|||0000-0002-6045-5627 Cordero Casanovas, Alex|||0000-0002-2224-7122 Gómez-Miragaya, Jorge|||0000-0003-1801-4681 Palomero, Luis|||0000-0002-9144-1017 Gomez-Caamaño, Antonio|||0000-0002-9773-4590 Gajewski, Thomas F. Cohen, Ezra E. W. Jesiotr, Marzena Bodnar, Lubomir Quintela-Fandino, Miguel|||0000-0003-1648-1964 Lopez-Bigas, Nuria|||0000-0003-4925-8988 Valdés-Mas, Rafael Puente, Xose S.|||0000-0001-9525-1483 Viñals, Francesc|||0000-0002-9918-6751 Casanovas, Oriol|||0000-0002-4298-3995 Graupera, Mariona|||0000-0003-4608-4185 Hernandez-Losa, Javier|||0000-0003-1526-3201 Ramón y Cajal, Santiago|||0000-0002-3867-1390 Garcia-Alonso, Luz|||0000-0002-7863-9619 Saez-Rodriguez, J. Esteller, M.|||0000-0003-4490-6093 Sierra-Jimenez, Angels|||0000-0003-1023-3492 Martín-Martín, Natalia|||0000-0002-2527-429X Matheu Fernandez, Ander Carracedo, Arkaitz|||0000-0001-5957-1260 González-Suárez, Eva|||0000-0003-0858-8171 Nanjundan, Meera Cortés Castán, Javier|||0000-0001-7623-1583 Lázaro García, Conxi|||0000-0002-7198-5906 Odero, Maria D.|||0000-0002-8858-2054 Martens, John W. M. Moreno-Bueno, Gema Barcellos-Hoff, Mary Helen Villanueva, Alejandro|||0000-0001-5164-0006 Gomis, Roger R.|||0000-0001-6473-2858 Pujana, Miguel Angel|||0000-0003-3222-4044 |
| author |
Mateo, Francesca|||0000-0002-2342-7010 |
| author_facet |
Mateo, Francesca|||0000-0002-2342-7010 Arenas, Enrique J.|||0000-0001-7076-2666 Aguilar, Helena Serra-Musach, Jordi Ruiz de Garibay, Gorka|||0000-0001-9936-8419 Boni, Jacopo|||0000-0003-2626-9393 Maicas, Miren|||0000-0003-1404-5552 Du, Shisuo Iorio, Francesco|||0000-0001-7063-8913 Herranz-Ors, Carmen|||0000-0002-2866-0321 Islam, Abul Prado, X. Llorente, Alicia Petit Montserrat, Anna|||0000-0002-9284-095X Vidal, August|||0000-0001-5727-2099 Català, Isabel Soler, Teresa Venturas, G. Rojo-Sebastian, Alejandro|||0000-0001-6439-3518 Serra, Helena Cuadras, Daniel|||0000-0001-8780-1764 Blanco Guillermo, Ignacio|||0000-0002-7414-7481 Lozano, José Canals, Francesc|||0000-0002-0650-1135 Sieuwerts, Anieta M. De Weerd, Vanja Look, Maxime P. Puertas, Sara García, Nadia Perkins, Archibald S. Bonifaci, Núria|||0000-0002-8193-6825 Skowron, Margaretha A. Gómez-Baldó, Laia Hernández, Vanessa Martínez-Aranda, Antonio Martínez-Iniesta, Maria|||0000-0001-6252-6671 Serrat Farran, Xènia|||0000-0001-7611-5400 Cerón, Julián|||0000-0003-4739-2243 Brunet, Joan|||0000-0003-1945-3512 Barretina-Ginesta, Maria-Pilar|||0000-0003-0074-6614 Gil, Mercedes|||0000-0002-7387-2139 Falo, Catalina|||0000-0002-5714-6823 Fernández, Adela Morilla, Idoia Pernas, Sonia|||0000-0002-1485-5080 Plà, Maria Jesus Andreu, Xavier Seguí Palmer, Miguel Ángel|||0000-0002-5103-6746 Ballester, Rosa|||0000-0002-7870-4185 Castellà Fernández, Eva Nellist, Mark D. Morales, Saleta Valls, Joan|||0000-0002-4806-7568 Velasco Sánchez, Ana Matías-Guiu, Xavier|||0000-0002-7201-6605 Figueras, Agnes Sánchez-Mut, José Vicente|||0000-0002-9292-8521 Sánchez Céspedes, Montse|||0000-0002-6045-5627 Cordero Casanovas, Alex|||0000-0002-2224-7122 Gómez-Miragaya, Jorge|||0000-0003-1801-4681 Palomero, Luis|||0000-0002-9144-1017 Gomez-Caamaño, Antonio|||0000-0002-9773-4590 Gajewski, Thomas F. Cohen, Ezra E. W. Jesiotr, Marzena Bodnar, Lubomir Quintela-Fandino, Miguel|||0000-0003-1648-1964 Lopez-Bigas, Nuria|||0000-0003-4925-8988 Valdés-Mas, Rafael Puente, Xose S.|||0000-0001-9525-1483 Viñals, Francesc|||0000-0002-9918-6751 Casanovas, Oriol|||0000-0002-4298-3995 Graupera, Mariona|||0000-0003-4608-4185 Hernandez-Losa, Javier|||0000-0003-1526-3201 Ramón y Cajal, Santiago|||0000-0002-3867-1390 Garcia-Alonso, Luz|||0000-0002-7863-9619 Saez-Rodriguez, J. Esteller, M.|||0000-0003-4490-6093 Sierra-Jimenez, Angels|||0000-0003-1023-3492 Martín-Martín, Natalia|||0000-0002-2527-429X Matheu Fernandez, Ander Carracedo, Arkaitz|||0000-0001-5957-1260 González-Suárez, Eva|||0000-0003-0858-8171 Nanjundan, Meera Cortés Castán, Javier|||0000-0001-7623-1583 Lázaro García, Conxi|||0000-0002-7198-5906 Odero, Maria D.|||0000-0002-8858-2054 Martens, John W. M. Moreno-Bueno, Gema Barcellos-Hoff, Mary Helen Villanueva, Alejandro|||0000-0001-5164-0006 Gomis, Roger R.|||0000-0001-6473-2858 Pujana, Miguel Angel|||0000-0003-3222-4044 |
| author_role |
author |
| author2 |
Arenas, Enrique J.|||0000-0001-7076-2666 Aguilar, Helena Serra-Musach, Jordi Ruiz de Garibay, Gorka|||0000-0001-9936-8419 Boni, Jacopo|||0000-0003-2626-9393 Maicas, Miren|||0000-0003-1404-5552 Du, Shisuo Iorio, Francesco|||0000-0001-7063-8913 Herranz-Ors, Carmen|||0000-0002-2866-0321 Islam, Abul Prado, X. Llorente, Alicia Petit Montserrat, Anna|||0000-0002-9284-095X Vidal, August|||0000-0001-5727-2099 Català, Isabel Soler, Teresa Venturas, G. Rojo-Sebastian, Alejandro|||0000-0001-6439-3518 Serra, Helena Cuadras, Daniel|||0000-0001-8780-1764 Blanco Guillermo, Ignacio|||0000-0002-7414-7481 Lozano, José Canals, Francesc|||0000-0002-0650-1135 Sieuwerts, Anieta M. De Weerd, Vanja Look, Maxime P. Puertas, Sara García, Nadia Perkins, Archibald S. Bonifaci, Núria|||0000-0002-8193-6825 Skowron, Margaretha A. Gómez-Baldó, Laia Hernández, Vanessa Martínez-Aranda, Antonio Martínez-Iniesta, Maria|||0000-0001-6252-6671 Serrat Farran, Xènia|||0000-0001-7611-5400 Cerón, Julián|||0000-0003-4739-2243 Brunet, Joan|||0000-0003-1945-3512 Barretina-Ginesta, Maria-Pilar|||0000-0003-0074-6614 Gil, Mercedes|||0000-0002-7387-2139 Falo, Catalina|||0000-0002-5714-6823 Fernández, Adela Morilla, Idoia Pernas, Sonia|||0000-0002-1485-5080 Plà, Maria Jesus Andreu, Xavier Seguí Palmer, Miguel Ángel|||0000-0002-5103-6746 Ballester, Rosa|||0000-0002-7870-4185 Castellà Fernández, Eva Nellist, Mark D. Morales, Saleta Valls, Joan|||0000-0002-4806-7568 Velasco Sánchez, Ana Matías-Guiu, Xavier|||0000-0002-7201-6605 Figueras, Agnes Sánchez-Mut, José Vicente|||0000-0002-9292-8521 Sánchez Céspedes, Montse|||0000-0002-6045-5627 Cordero Casanovas, Alex|||0000-0002-2224-7122 Gómez-Miragaya, Jorge|||0000-0003-1801-4681 Palomero, Luis|||0000-0002-9144-1017 Gomez-Caamaño, Antonio|||0000-0002-9773-4590 Gajewski, Thomas F. Cohen, Ezra E. W. Jesiotr, Marzena Bodnar, Lubomir Quintela-Fandino, Miguel|||0000-0003-1648-1964 Lopez-Bigas, Nuria|||0000-0003-4925-8988 Valdés-Mas, Rafael Puente, Xose S.|||0000-0001-9525-1483 Viñals, Francesc|||0000-0002-9918-6751 Casanovas, Oriol|||0000-0002-4298-3995 Graupera, Mariona|||0000-0003-4608-4185 Hernandez-Losa, Javier|||0000-0003-1526-3201 Ramón y Cajal, Santiago|||0000-0002-3867-1390 Garcia-Alonso, Luz|||0000-0002-7863-9619 Saez-Rodriguez, J. Esteller, M.|||0000-0003-4490-6093 Sierra-Jimenez, Angels|||0000-0003-1023-3492 Martín-Martín, Natalia|||0000-0002-2527-429X Matheu Fernandez, Ander Carracedo, Arkaitz|||0000-0001-5957-1260 González-Suárez, Eva|||0000-0003-0858-8171 Nanjundan, Meera Cortés Castán, Javier|||0000-0001-7623-1583 Lázaro García, Conxi|||0000-0002-7198-5906 Odero, Maria D.|||0000-0002-8858-2054 Martens, John W. M. Moreno-Bueno, Gema Barcellos-Hoff, Mary Helen Villanueva, Alejandro|||0000-0001-5164-0006 Gomis, Roger R.|||0000-0001-6473-2858 Pujana, Miguel Angel|||0000-0003-3222-4044 |
| 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 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 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 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 |
Adaptor Proteins, Signal Transducing Adult Aged Breast Neoplasms Carrier Proteins Cell Proliferation DNA-Binding Proteins Female Gene Expression Regulation, Neoplastic Humans Lung Neoplasms MCF-7 Cells Microfilament Proteins Middle Aged Neoplasm Metastasis Osteonectin Proto-Oncogenes Signal Transduction SOX9 Transcription Factor TOR Serine-Threonine Kinases Transcription Factors Xenograft Model Antitumor Assays |
| topic |
Adaptor Proteins, Signal Transducing Adult Aged Breast Neoplasms Carrier Proteins Cell Proliferation DNA-Binding Proteins Female Gene Expression Regulation, Neoplastic Humans Lung Neoplasms MCF-7 Cells Microfilament Proteins Middle Aged Neoplasm Metastasis Osteonectin Proto-Oncogenes Signal Transduction SOX9 Transcription Factor TOR Serine-Threonine Kinases Transcription Factors Xenograft Model Antitumor Assays |
| description |
Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure. |
| 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/291146 https://dx.doi.org/urn:doi:10.1038/onc.2016.427 |
| url |
https://ddd.uab.cat/record/291146 https://dx.doi.org/urn:doi:10.1038/onc.2016.427 |
| 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 SAF2010-20203 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/01528 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI13/00132 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/00336 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0036/0008 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0036/0063 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2013-46196 Ministerio de Sanidad y Consumo RD06/0020/1051 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| 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-nc-nd/4.0/ |
| 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 |
|
| _version_ |
1869414997874966528 |
| spelling |
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibitionMateo, Francesca|||0000-0002-2342-7010Arenas, Enrique J.|||0000-0001-7076-2666Aguilar, HelenaSerra-Musach, JordiRuiz de Garibay, Gorka|||0000-0001-9936-8419Boni, Jacopo|||0000-0003-2626-9393Maicas, Miren|||0000-0003-1404-5552Du, ShisuoIorio, Francesco|||0000-0001-7063-8913Herranz-Ors, Carmen|||0000-0002-2866-0321Islam, AbulPrado, X.Llorente, AliciaPetit Montserrat, Anna|||0000-0002-9284-095XVidal, August|||0000-0001-5727-2099Català, IsabelSoler, TeresaVenturas, G.Rojo-Sebastian, Alejandro|||0000-0001-6439-3518Serra, HelenaCuadras, Daniel|||0000-0001-8780-1764Blanco Guillermo, Ignacio|||0000-0002-7414-7481Lozano, JoséCanals, Francesc|||0000-0002-0650-1135Sieuwerts, Anieta M.De Weerd, VanjaLook, Maxime P.Puertas, SaraGarcía, NadiaPerkins, Archibald S.Bonifaci, Núria|||0000-0002-8193-6825Skowron, Margaretha A.Gómez-Baldó, LaiaHernández, VanessaMartínez-Aranda, AntonioMartínez-Iniesta, Maria|||0000-0001-6252-6671Serrat Farran, Xènia|||0000-0001-7611-5400Cerón, Julián|||0000-0003-4739-2243Brunet, Joan|||0000-0003-1945-3512Barretina-Ginesta, Maria-Pilar|||0000-0003-0074-6614Gil, Mercedes|||0000-0002-7387-2139Falo, Catalina|||0000-0002-5714-6823Fernández, AdelaMorilla, IdoiaPernas, Sonia|||0000-0002-1485-5080Plà, Maria JesusAndreu, XavierSeguí Palmer, Miguel Ángel|||0000-0002-5103-6746Ballester, Rosa|||0000-0002-7870-4185Castellà Fernández, EvaNellist, Mark D.Morales, SaletaValls, Joan|||0000-0002-4806-7568Velasco Sánchez, AnaMatías-Guiu, Xavier|||0000-0002-7201-6605Figueras, AgnesSánchez-Mut, José Vicente|||0000-0002-9292-8521Sánchez Céspedes, Montse|||0000-0002-6045-5627Cordero Casanovas, Alex|||0000-0002-2224-7122Gómez-Miragaya, Jorge|||0000-0003-1801-4681Palomero, Luis|||0000-0002-9144-1017Gomez-Caamaño, Antonio|||0000-0002-9773-4590Gajewski, Thomas F.Cohen, Ezra E. W.Jesiotr, MarzenaBodnar, LubomirQuintela-Fandino, Miguel|||0000-0003-1648-1964Lopez-Bigas, Nuria|||0000-0003-4925-8988Valdés-Mas, RafaelPuente, Xose S.|||0000-0001-9525-1483Viñals, Francesc|||0000-0002-9918-6751Casanovas, Oriol|||0000-0002-4298-3995Graupera, Mariona|||0000-0003-4608-4185Hernandez-Losa, Javier|||0000-0003-1526-3201Ramón y Cajal, Santiago|||0000-0002-3867-1390Garcia-Alonso, Luz|||0000-0002-7863-9619Saez-Rodriguez, J.Esteller, M.|||0000-0003-4490-6093Sierra-Jimenez, Angels|||0000-0003-1023-3492Martín-Martín, Natalia|||0000-0002-2527-429XMatheu Fernandez, AnderCarracedo, Arkaitz|||0000-0001-5957-1260González-Suárez, Eva|||0000-0003-0858-8171Nanjundan, MeeraCortés Castán, Javier|||0000-0001-7623-1583Lázaro García, Conxi|||0000-0002-7198-5906Odero, Maria D.|||0000-0002-8858-2054Martens, John W. M.Moreno-Bueno, GemaBarcellos-Hoff, Mary HelenVillanueva, Alejandro|||0000-0001-5164-0006Gomis, Roger R.|||0000-0001-6473-2858Pujana, Miguel Angel|||0000-0003-3222-4044Adaptor Proteins, Signal TransducingAdultAgedBreast NeoplasmsCarrier ProteinsCell ProliferationDNA-Binding ProteinsFemaleGene Expression Regulation, NeoplasticHumansLung NeoplasmsMCF-7 CellsMicrofilament ProteinsMiddle AgedNeoplasm MetastasisOsteonectinProto-OncogenesSignal TransductionSOX9 Transcription FactorTOR Serine-Threonine KinasesTranscription FactorsXenograft Model Antitumor AssaysInhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.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/291146https://dx.doi.org/urn:doi:10.1038/onc.2016.427reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia e Innovación https://doi.org/10.13039/501100004837 SAF2010-20203Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/01528Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI13/00132Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/00336Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0036/0008Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0036/0063Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2013-46196Ministerio de Sanidad y Consumo RD06/0020/1051open 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, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2911462026-06-06T12:50:31Z |
| score |
15,300719 |