MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis
MAF amplification increases the risk of breast cancer (BCa) metastasis through mechanisms that are still poorly understood yet have important clinical implications. Oestrogen-receptor-positive (ER + ) BCa requires oestrogen for both growth and metastasis, albeit by ill-known mechanisms. Here we inte...
Gespeichert in:
| Veröffentlicht in: | Nature cell biology 2023-12, Vol.25 (12), p.1833-1847 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1847 |
|---|---|
| container_issue | 12 |
| container_start_page | 1833 |
| container_title | Nature cell biology |
| container_volume | 25 |
| creator | Llorente, Alicia Blasco, María Teresa Espuny, Irene Guiu, Marc Ballaré, Cecilia Blanco, Enrique Caballé, Adrià Bellmunt, Anna Salvador, Fernando Morales, Andrea Nuñez, Marc Loren, Guillem Imbastari, Francesca Fidalgo, Marta Figueras-Puig, Cristina Gibler, Patrizia Graupera, Mariona Monteiro, Freddy Riera, Antoni Holen, Ingunn Avgustinova, Alexandra Di Croce, Luciano Gomis, Roger R. |
| description | MAF
amplification increases the risk of breast cancer (BCa) metastasis through mechanisms that are still poorly understood yet have important clinical implications. Oestrogen-receptor-positive (ER
+
) BCa requires oestrogen for both growth and metastasis, albeit by ill-known mechanisms. Here we integrate proteomics, transcriptomics, epigenomics, chromatin accessibility and functional assays from human and syngeneic mouse BCa models to show that MAF directly interacts with oestrogen receptor alpha (ERα), thereby promoting a unique chromatin landscape that favours metastatic spread. We identify metastasis-promoting genes that are de novo licensed following oestrogen exposure in a MAF-dependent manner. The histone demethylase KDM1A is key to the epigenomic remodelling that facilitates the expression of the pro-metastatic MAF/oestrogen-driven gene expression program, and loss of KDM1A activity prevents this metastasis. We have thus determined that the molecular basis underlying MAF/oestrogen-mediated metastasis requires genetic, epigenetic and hormone signals from the systemic environment, which influence the ability of BCa cells to metastasize.
Llorente, Blasco, Espuny and colleagues show that MAF regulates the genomic distribution of ERα and modulates the expression of metastasis genes via KDM1A, thereby driving metastatic spread in breast cancer. |
| doi_str_mv | 10.1038/s41556-023-01281-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10709142</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2889240761</sourcerecordid><originalsourceid>FETCH-LOGICAL-c426t-63cd49aca14a7e5bd47427a67bdbef823dca2ffef45cc515c66522841016dc9a3</originalsourceid><addsrcrecordid>eNp9kc1u1TAQhS0EoqXwAiyQJTZsArbjn3iFqqoFpKJKFayN40xyXSX2xXYq3cfiRXgm3N5SfhZdeaz55thnDkIvKXlLSdu9y5wKIRvC2oZQ1tFm9wgdUq5kw6XSj29qKRrVanaAnuV8RQjlnKin6KBVmgtN-CH69vn4DNtlO_vRO1t8DHj2DkKGjE8vf_7AZZPiOm0wbP0EAYp3OMESB5hnHyZcIh6SvwbcJ7C5YGeDg4QXKPVms8_P0ZPRzhle3J1H6OvZ6ZeTj835xYdPJ8fnjeNMlka2buDaOku5VSD6gSvOlJWqH3oYO9YOzrJxhJEL5wQVTkrBWMcpoXJw2rZH6P1ed7v2CwzVQkl2NtvkF5t2Jlpv_u0EvzFTvDaUKKIpZ1XhzZ1Cit9XyMUsPrvq0waIazas6zSr-5O0oq__Q6_imkL1VymthRBcyEqxPeVSzDnBeP8bSsxNgmafoKkJmtsEza4Ovfrbx_3I78gq0O6BXFthgvTn7QdkfwFWjKpN</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2899555456</pqid></control><display><type>article</type><title>MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>Nature Journals Online</source><creator>Llorente, Alicia ; Blasco, María Teresa ; Espuny, Irene ; Guiu, Marc ; Ballaré, Cecilia ; Blanco, Enrique ; Caballé, Adrià ; Bellmunt, Anna ; Salvador, Fernando ; Morales, Andrea ; Nuñez, Marc ; Loren, Guillem ; Imbastari, Francesca ; Fidalgo, Marta ; Figueras-Puig, Cristina ; Gibler, Patrizia ; Graupera, Mariona ; Monteiro, Freddy ; Riera, Antoni ; Holen, Ingunn ; Avgustinova, Alexandra ; Di Croce, Luciano ; Gomis, Roger R.</creator><creatorcontrib>Llorente, Alicia ; Blasco, María Teresa ; Espuny, Irene ; Guiu, Marc ; Ballaré, Cecilia ; Blanco, Enrique ; Caballé, Adrià ; Bellmunt, Anna ; Salvador, Fernando ; Morales, Andrea ; Nuñez, Marc ; Loren, Guillem ; Imbastari, Francesca ; Fidalgo, Marta ; Figueras-Puig, Cristina ; Gibler, Patrizia ; Graupera, Mariona ; Monteiro, Freddy ; Riera, Antoni ; Holen, Ingunn ; Avgustinova, Alexandra ; Di Croce, Luciano ; Gomis, Roger R.</creatorcontrib><description>MAF
amplification increases the risk of breast cancer (BCa) metastasis through mechanisms that are still poorly understood yet have important clinical implications. Oestrogen-receptor-positive (ER
+
) BCa requires oestrogen for both growth and metastasis, albeit by ill-known mechanisms. Here we integrate proteomics, transcriptomics, epigenomics, chromatin accessibility and functional assays from human and syngeneic mouse BCa models to show that MAF directly interacts with oestrogen receptor alpha (ERα), thereby promoting a unique chromatin landscape that favours metastatic spread. We identify metastasis-promoting genes that are de novo licensed following oestrogen exposure in a MAF-dependent manner. The histone demethylase KDM1A is key to the epigenomic remodelling that facilitates the expression of the pro-metastatic MAF/oestrogen-driven gene expression program, and loss of KDM1A activity prevents this metastasis. We have thus determined that the molecular basis underlying MAF/oestrogen-mediated metastasis requires genetic, epigenetic and hormone signals from the systemic environment, which influence the ability of BCa cells to metastasize.
Llorente, Blasco, Espuny and colleagues show that MAF regulates the genomic distribution of ERα and modulates the expression of metastasis genes via KDM1A, thereby driving metastatic spread in breast cancer.</description><identifier>ISSN: 1465-7392</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/s41556-023-01281-y</identifier><identifier>PMID: 37945904</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>14/19 ; 38/39 ; 38/91 ; 45/15 ; 59/5 ; 631/67/1347 ; 631/67/322 ; 631/67/68/2486 ; 64/60 ; 82/58 ; Amplification ; Animal models ; Animals ; Biomedical and Life Sciences ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Cancer Research ; Cell Biology ; Cell Line, Tumor ; Chromatin ; Developmental Biology ; Epigenesis, Genetic ; Epigenetics ; Estrogen Receptor alpha - genetics ; Estrogen Receptor alpha - metabolism ; Estrogen receptors ; Estrogens ; Female ; Gene Amplification ; Gene expression ; Genes ; Histone Demethylases - genetics ; Histone Demethylases - metabolism ; Histones ; Humans ; Life Sciences ; Metastases ; Metastasis ; Mice ; Proteomics ; Proto-Oncogene Proteins c-maf - genetics ; Receptors ; Stem Cells ; Transcriptomics</subject><ispartof>Nature cell biology, 2023-12, Vol.25 (12), p.1833-1847</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c426t-63cd49aca14a7e5bd47427a67bdbef823dca2ffef45cc515c66522841016dc9a3</cites><orcidid>0000-0002-8759-6913 ; 0000-0003-1906-4947 ; 0000-0003-4457-6864 ; 0000-0002-7083-986X ; 0000-0001-9531-2522 ; 0000-0003-4100-4318 ; 0000-0001-6261-7370 ; 0000-0002-6056-0566 ; 0000-0001-6473-2858 ; 0000-0003-4608-4185 ; 0000-0002-6794-0473 ; 0000-0001-7142-7675 ; 0000-0002-9080-6715 ; 0000-0002-2388-4713</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41556-023-01281-y$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41556-023-01281-y$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37945904$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Llorente, Alicia</creatorcontrib><creatorcontrib>Blasco, María Teresa</creatorcontrib><creatorcontrib>Espuny, Irene</creatorcontrib><creatorcontrib>Guiu, Marc</creatorcontrib><creatorcontrib>Ballaré, Cecilia</creatorcontrib><creatorcontrib>Blanco, Enrique</creatorcontrib><creatorcontrib>Caballé, Adrià</creatorcontrib><creatorcontrib>Bellmunt, Anna</creatorcontrib><creatorcontrib>Salvador, Fernando</creatorcontrib><creatorcontrib>Morales, Andrea</creatorcontrib><creatorcontrib>Nuñez, Marc</creatorcontrib><creatorcontrib>Loren, Guillem</creatorcontrib><creatorcontrib>Imbastari, Francesca</creatorcontrib><creatorcontrib>Fidalgo, Marta</creatorcontrib><creatorcontrib>Figueras-Puig, Cristina</creatorcontrib><creatorcontrib>Gibler, Patrizia</creatorcontrib><creatorcontrib>Graupera, Mariona</creatorcontrib><creatorcontrib>Monteiro, Freddy</creatorcontrib><creatorcontrib>Riera, Antoni</creatorcontrib><creatorcontrib>Holen, Ingunn</creatorcontrib><creatorcontrib>Avgustinova, Alexandra</creatorcontrib><creatorcontrib>Di Croce, Luciano</creatorcontrib><creatorcontrib>Gomis, Roger R.</creatorcontrib><title>MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>MAF
amplification increases the risk of breast cancer (BCa) metastasis through mechanisms that are still poorly understood yet have important clinical implications. Oestrogen-receptor-positive (ER
+
) BCa requires oestrogen for both growth and metastasis, albeit by ill-known mechanisms. Here we integrate proteomics, transcriptomics, epigenomics, chromatin accessibility and functional assays from human and syngeneic mouse BCa models to show that MAF directly interacts with oestrogen receptor alpha (ERα), thereby promoting a unique chromatin landscape that favours metastatic spread. We identify metastasis-promoting genes that are de novo licensed following oestrogen exposure in a MAF-dependent manner. The histone demethylase KDM1A is key to the epigenomic remodelling that facilitates the expression of the pro-metastatic MAF/oestrogen-driven gene expression program, and loss of KDM1A activity prevents this metastasis. We have thus determined that the molecular basis underlying MAF/oestrogen-mediated metastasis requires genetic, epigenetic and hormone signals from the systemic environment, which influence the ability of BCa cells to metastasize.
Llorente, Blasco, Espuny and colleagues show that MAF regulates the genomic distribution of ERα and modulates the expression of metastasis genes via KDM1A, thereby driving metastatic spread in breast cancer.</description><subject>14/19</subject><subject>38/39</subject><subject>38/91</subject><subject>45/15</subject><subject>59/5</subject><subject>631/67/1347</subject><subject>631/67/322</subject><subject>631/67/68/2486</subject><subject>64/60</subject><subject>82/58</subject><subject>Amplification</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Chromatin</subject><subject>Developmental Biology</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Estrogen Receptor alpha - genetics</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Female</subject><subject>Gene Amplification</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Histone Demethylases - genetics</subject><subject>Histone Demethylases - metabolism</subject><subject>Histones</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Proteomics</subject><subject>Proto-Oncogene Proteins c-maf - genetics</subject><subject>Receptors</subject><subject>Stem Cells</subject><subject>Transcriptomics</subject><issn>1465-7392</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc1u1TAQhS0EoqXwAiyQJTZsArbjn3iFqqoFpKJKFayN40xyXSX2xXYq3cfiRXgm3N5SfhZdeaz55thnDkIvKXlLSdu9y5wKIRvC2oZQ1tFm9wgdUq5kw6XSj29qKRrVanaAnuV8RQjlnKin6KBVmgtN-CH69vn4DNtlO_vRO1t8DHj2DkKGjE8vf_7AZZPiOm0wbP0EAYp3OMESB5hnHyZcIh6SvwbcJ7C5YGeDg4QXKPVms8_P0ZPRzhle3J1H6OvZ6ZeTj835xYdPJ8fnjeNMlka2buDaOku5VSD6gSvOlJWqH3oYO9YOzrJxhJEL5wQVTkrBWMcpoXJw2rZH6P1ed7v2CwzVQkl2NtvkF5t2Jlpv_u0EvzFTvDaUKKIpZ1XhzZ1Cit9XyMUsPrvq0waIazas6zSr-5O0oq__Q6_imkL1VymthRBcyEqxPeVSzDnBeP8bSsxNgmafoKkJmtsEza4Ovfrbx_3I78gq0O6BXFthgvTn7QdkfwFWjKpN</recordid><startdate>20231201</startdate><enddate>20231201</enddate><creator>Llorente, Alicia</creator><creator>Blasco, María Teresa</creator><creator>Espuny, Irene</creator><creator>Guiu, Marc</creator><creator>Ballaré, Cecilia</creator><creator>Blanco, Enrique</creator><creator>Caballé, Adrià</creator><creator>Bellmunt, Anna</creator><creator>Salvador, Fernando</creator><creator>Morales, Andrea</creator><creator>Nuñez, Marc</creator><creator>Loren, Guillem</creator><creator>Imbastari, Francesca</creator><creator>Fidalgo, Marta</creator><creator>Figueras-Puig, Cristina</creator><creator>Gibler, Patrizia</creator><creator>Graupera, Mariona</creator><creator>Monteiro, Freddy</creator><creator>Riera, Antoni</creator><creator>Holen, Ingunn</creator><creator>Avgustinova, Alexandra</creator><creator>Di Croce, Luciano</creator><creator>Gomis, Roger R.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8759-6913</orcidid><orcidid>https://orcid.org/0000-0003-1906-4947</orcidid><orcidid>https://orcid.org/0000-0003-4457-6864</orcidid><orcidid>https://orcid.org/0000-0002-7083-986X</orcidid><orcidid>https://orcid.org/0000-0001-9531-2522</orcidid><orcidid>https://orcid.org/0000-0003-4100-4318</orcidid><orcidid>https://orcid.org/0000-0001-6261-7370</orcidid><orcidid>https://orcid.org/0000-0002-6056-0566</orcidid><orcidid>https://orcid.org/0000-0001-6473-2858</orcidid><orcidid>https://orcid.org/0000-0003-4608-4185</orcidid><orcidid>https://orcid.org/0000-0002-6794-0473</orcidid><orcidid>https://orcid.org/0000-0001-7142-7675</orcidid><orcidid>https://orcid.org/0000-0002-9080-6715</orcidid><orcidid>https://orcid.org/0000-0002-2388-4713</orcidid></search><sort><creationdate>20231201</creationdate><title>MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis</title><author>Llorente, Alicia ; Blasco, María Teresa ; Espuny, Irene ; Guiu, Marc ; Ballaré, Cecilia ; Blanco, Enrique ; Caballé, Adrià ; Bellmunt, Anna ; Salvador, Fernando ; Morales, Andrea ; Nuñez, Marc ; Loren, Guillem ; Imbastari, Francesca ; Fidalgo, Marta ; Figueras-Puig, Cristina ; Gibler, Patrizia ; Graupera, Mariona ; Monteiro, Freddy ; Riera, Antoni ; Holen, Ingunn ; Avgustinova, Alexandra ; Di Croce, Luciano ; Gomis, Roger R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-63cd49aca14a7e5bd47427a67bdbef823dca2ffef45cc515c66522841016dc9a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>14/19</topic><topic>38/39</topic><topic>38/91</topic><topic>45/15</topic><topic>59/5</topic><topic>631/67/1347</topic><topic>631/67/322</topic><topic>631/67/68/2486</topic><topic>64/60</topic><topic>82/58</topic><topic>Amplification</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer Research</topic><topic>Cell Biology</topic><topic>Cell Line, Tumor</topic><topic>Chromatin</topic><topic>Developmental Biology</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Estrogen Receptor alpha - genetics</topic><topic>Estrogen Receptor alpha - metabolism</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>Female</topic><topic>Gene Amplification</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Histone Demethylases - genetics</topic><topic>Histone Demethylases - metabolism</topic><topic>Histones</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Proteomics</topic><topic>Proto-Oncogene Proteins c-maf - genetics</topic><topic>Receptors</topic><topic>Stem Cells</topic><topic>Transcriptomics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Llorente, Alicia</creatorcontrib><creatorcontrib>Blasco, María Teresa</creatorcontrib><creatorcontrib>Espuny, Irene</creatorcontrib><creatorcontrib>Guiu, Marc</creatorcontrib><creatorcontrib>Ballaré, Cecilia</creatorcontrib><creatorcontrib>Blanco, Enrique</creatorcontrib><creatorcontrib>Caballé, Adrià</creatorcontrib><creatorcontrib>Bellmunt, Anna</creatorcontrib><creatorcontrib>Salvador, Fernando</creatorcontrib><creatorcontrib>Morales, Andrea</creatorcontrib><creatorcontrib>Nuñez, Marc</creatorcontrib><creatorcontrib>Loren, Guillem</creatorcontrib><creatorcontrib>Imbastari, Francesca</creatorcontrib><creatorcontrib>Fidalgo, Marta</creatorcontrib><creatorcontrib>Figueras-Puig, Cristina</creatorcontrib><creatorcontrib>Gibler, Patrizia</creatorcontrib><creatorcontrib>Graupera, Mariona</creatorcontrib><creatorcontrib>Monteiro, Freddy</creatorcontrib><creatorcontrib>Riera, Antoni</creatorcontrib><creatorcontrib>Holen, Ingunn</creatorcontrib><creatorcontrib>Avgustinova, Alexandra</creatorcontrib><creatorcontrib>Di Croce, Luciano</creatorcontrib><creatorcontrib>Gomis, Roger R.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Llorente, Alicia</au><au>Blasco, María Teresa</au><au>Espuny, Irene</au><au>Guiu, Marc</au><au>Ballaré, Cecilia</au><au>Blanco, Enrique</au><au>Caballé, Adrià</au><au>Bellmunt, Anna</au><au>Salvador, Fernando</au><au>Morales, Andrea</au><au>Nuñez, Marc</au><au>Loren, Guillem</au><au>Imbastari, Francesca</au><au>Fidalgo, Marta</au><au>Figueras-Puig, Cristina</au><au>Gibler, Patrizia</au><au>Graupera, Mariona</au><au>Monteiro, Freddy</au><au>Riera, Antoni</au><au>Holen, Ingunn</au><au>Avgustinova, Alexandra</au><au>Di Croce, Luciano</au><au>Gomis, Roger R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2023-12-01</date><risdate>2023</risdate><volume>25</volume><issue>12</issue><spage>1833</spage><epage>1847</epage><pages>1833-1847</pages><issn>1465-7392</issn><eissn>1476-4679</eissn><abstract>MAF
amplification increases the risk of breast cancer (BCa) metastasis through mechanisms that are still poorly understood yet have important clinical implications. Oestrogen-receptor-positive (ER
+
) BCa requires oestrogen for both growth and metastasis, albeit by ill-known mechanisms. Here we integrate proteomics, transcriptomics, epigenomics, chromatin accessibility and functional assays from human and syngeneic mouse BCa models to show that MAF directly interacts with oestrogen receptor alpha (ERα), thereby promoting a unique chromatin landscape that favours metastatic spread. We identify metastasis-promoting genes that are de novo licensed following oestrogen exposure in a MAF-dependent manner. The histone demethylase KDM1A is key to the epigenomic remodelling that facilitates the expression of the pro-metastatic MAF/oestrogen-driven gene expression program, and loss of KDM1A activity prevents this metastasis. We have thus determined that the molecular basis underlying MAF/oestrogen-mediated metastasis requires genetic, epigenetic and hormone signals from the systemic environment, which influence the ability of BCa cells to metastasize.
Llorente, Blasco, Espuny and colleagues show that MAF regulates the genomic distribution of ERα and modulates the expression of metastasis genes via KDM1A, thereby driving metastatic spread in breast cancer.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>37945904</pmid><doi>10.1038/s41556-023-01281-y</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-8759-6913</orcidid><orcidid>https://orcid.org/0000-0003-1906-4947</orcidid><orcidid>https://orcid.org/0000-0003-4457-6864</orcidid><orcidid>https://orcid.org/0000-0002-7083-986X</orcidid><orcidid>https://orcid.org/0000-0001-9531-2522</orcidid><orcidid>https://orcid.org/0000-0003-4100-4318</orcidid><orcidid>https://orcid.org/0000-0001-6261-7370</orcidid><orcidid>https://orcid.org/0000-0002-6056-0566</orcidid><orcidid>https://orcid.org/0000-0001-6473-2858</orcidid><orcidid>https://orcid.org/0000-0003-4608-4185</orcidid><orcidid>https://orcid.org/0000-0002-6794-0473</orcidid><orcidid>https://orcid.org/0000-0001-7142-7675</orcidid><orcidid>https://orcid.org/0000-0002-9080-6715</orcidid><orcidid>https://orcid.org/0000-0002-2388-4713</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1465-7392 |
| ispartof | Nature cell biology, 2023-12, Vol.25 (12), p.1833-1847 |
| issn | 1465-7392 1476-4679 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10709142 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online |
| subjects | 14/19 38/39 38/91 45/15 59/5 631/67/1347 631/67/322 631/67/68/2486 64/60 82/58 Amplification Animal models Animals Biomedical and Life Sciences Breast cancer Breast Neoplasms - genetics Breast Neoplasms - pathology Cancer Research Cell Biology Cell Line, Tumor Chromatin Developmental Biology Epigenesis, Genetic Epigenetics Estrogen Receptor alpha - genetics Estrogen Receptor alpha - metabolism Estrogen receptors Estrogens Female Gene Amplification Gene expression Genes Histone Demethylases - genetics Histone Demethylases - metabolism Histones Humans Life Sciences Metastases Metastasis Mice Proteomics Proto-Oncogene Proteins c-maf - genetics Receptors Stem Cells Transcriptomics |
| title | MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T04%3A39%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=MAF%20amplification%20licenses%20ER%CE%B1%20through%20epigenetic%20remodelling%20to%20drive%20breast%20cancer%20metastasis&rft.jtitle=Nature%20cell%20biology&rft.au=Llorente,%20Alicia&rft.date=2023-12-01&rft.volume=25&rft.issue=12&rft.spage=1833&rft.epage=1847&rft.pages=1833-1847&rft.issn=1465-7392&rft.eissn=1476-4679&rft_id=info:doi/10.1038/s41556-023-01281-y&rft_dat=%3Cproquest_pubme%3E2889240761%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2899555456&rft_id=info:pmid/37945904&rfr_iscdi=true |