{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T11:19:24Z","timestamp":1788002364576,"version":"build-2784847793"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102022R1A2C2005094"],"award-info":[{"award-number":["NRF\u20102022R1A2C2005094"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Nutrient deprivation in the tumor microenvironment drives metastatic progression. However, its role in breast cancer metastasis and underlying epigenetic mechanisms remain unclear. We identify an enhancer\u2010driven transcriptional program that promotes breast cancer metastasis under nutrient deprivation. Transient glucose\u2013glutamine deprivation in MCF7 and MDA\u2010MB\u2010231 cells induces the expression of genes involved in migration, invasion, and metastasis. Chromatin immunoprecipitation sequencing shows distinct enhancer activation, marked by increased histone H3 lysine 27 and bromodomain\u2010containing protein 4 (BRD4) recruitment. Targeted enhancer acetylation using dCas9\u2013p300 increases cognate gene expression. Motif and CUT&amp;RUN analyses indicate the enrichment and direct binding of ATF3 and c\u2010JUN at enhancers\u2014essential for their activation. Transient transcriptome sequencing shows an increase in endothelin 1 (\n                    <jats:italic>EDN1<\/jats:italic>\n                    ) enhancer RNA (eRNA) transcription to facilitate enhancer activation, which is reduced by treatment with eRNA\u2010targeting antisense oligonucleotides (ASOs). In an orthotopic mouse model, BRD4 inhibition using JQ1 or MZ1 suppresses 4T1 cell metastasis.\n                    <jats:italic>EDN1<\/jats:italic>\n                    enhancer acetylation with dCas9\u2013p300 increases MCF7 tumor growth, which is reduced by BRD4 inhibition or ASO treatment. BRD4 and EDN1 expression is commonly upregulated in human breast metastasis. These findings define nutrient stress\u2010responsive enhancers as epigenetic drivers of metastatic adaptation and highlight their therapeutic potential in breast cancer.\n                  <\/jats:p>","DOI":"10.1002\/advs.77493","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T11:12:56Z","timestamp":1788001976000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glucose and Glutamine Deprivation Promotes Breast Cancer Lung Metastasis via BRD4\u2010Dependent Enhancer Activation"],"prefix":"10.1002","author":[{"given":"Poshan Yugal","family":"Bhattarai","sequence":"first","affiliation":[{"name":"Honam Regional Future Drug Development Convergence Education &amp; Research Division (BK21 FOUR) College of Pharmacy Chosun University Jeonnam\u2010Gwangju Special Metropolitan City 61452 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4616-2374","authenticated-orcid":false,"given":"Arathy","family":"Vasukutty","sequence":"additional","affiliation":[{"name":"Honam Regional Future Drug Development Convergence Education &amp; Research Division (BK21 FOUR) College of Pharmacy Chosun University Jeonnam\u2010Gwangju Special Metropolitan City 61452 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujin","family":"Na","sequence":"additional","affiliation":[{"name":"Honam Regional Future Drug Development Convergence Education &amp; Research Division (BK21 FOUR) College of Pharmacy Chosun University Jeonnam\u2010Gwangju Special Metropolitan City 61452 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung\u2010Chul","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Medicine Chosun University Jeonnam\u2010Gwangju Special Metropolitan City 61452 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7862-2342","authenticated-orcid":false,"given":"Hong Seok","family":"Choi","sequence":"additional","affiliation":[{"name":"Honam Regional Future Drug Development Convergence Education &amp; Research Division (BK21 FOUR) College of Pharmacy Chosun University Jeonnam\u2010Gwangju Special Metropolitan City 61452 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"issue":"34","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1038\/s41388-022-02408-5","article-title":"Glutamine Addiction Promotes Glucose Oxidation in Triple\u2010Negative Breast Cancer","volume":"41","author":"Quek L.\u2010E.","year":"2022","journal-title":"Oncogene"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2021.728759","article-title":"Glucose Metabolism and Glucose Transporters in Breast Cancer","volume":"9","author":"Shin E.","year":"2021","journal-title":"Frontiers in Cell and Developmental Biology"},{"issue":"1","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"4205","DOI":"10.1038\/s41467-020-18020-8","article-title":"GLUT1 Inhibition Blocks Growth of RB1\u2010Positive Triple Negative Breast Cancer","volume":"11","author":"Wu Q.","year":"2020","journal-title":"Nature Communications"},{"issue":"6","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/s41556-022-00919-7","article-title":"Cancer\u2010Cell\u2010Secreted Extracellular Vesicles Suppress Insulin Secretion Through miR\u2010122 to Impair Systemic Glucose Homeostasis and Contribute to Tumour Growth","volume":"24","author":"Cao M.","year":"2022","journal-title":"Nature Cell Biology"},{"issue":"10","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/ncb3410","article-title":"Regional Glutamine Deficiency in Tumours Promotes Dedifferentiation Through Inhibition of Histone\u00a0Demethylation","volume":"18","author":"Pan M.","year":"2016","journal-title":"Nature Cell Biology"},{"issue":"7","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1101\/gad.231894.113","article-title":"Stress\u2010Induced Cleavage of Myc Promotes Cancer Cell Survival","volume":"28","author":"Conacci\u2010Sorrell M.","year":"2014","journal-title":"Genes & Development"},{"issue":"10","key":"e_1_2_11_8_1","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2003014118","article-title":"Adaptation of Pancreatic Cancer Cells to Nutrient Deprivation is Reversible and Requires Glutamine Synthetase Stabilization by mTORC1","volume":"118","author":"Tsai P. 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