dc.contributor.author | Shechter, Ksenija Radic | |
dc.contributor.author | Kafkia, Eleni | |
dc.contributor.author | Zirngibl, Katharina | |
dc.contributor.author | Gawrzak, Sylwia | |
dc.contributor.author | Alladin, Ashna | |
dc.contributor.author | Machado, Daniel | |
dc.contributor.author | Lüchtenborg, Christian | |
dc.contributor.author | Sévin, Daniel C. | |
dc.contributor.author | Brügger, Britta | |
dc.contributor.author | Patil, Kiran R. | |
dc.contributor.author | Jechlinger, Martin | |
dc.date.accessioned | 2023-01-20T08:17:22Z | |
dc.date.available | 2023-01-20T08:17:22Z | |
dc.date.created | 2021-11-10T08:56:06Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Molecular Systems Biology. 2021, 17 . | en_US |
dc.identifier.issn | 1744-4292 | |
dc.identifier.uri | https://hdl.handle.net/11250/3044790 | |
dc.description.abstract | Tumor relapse from treatment-resistant cells (minimal residual disease, MRD) underlies most breast cancer-related deaths. Yet, the molecular characteristics defining their malignancy have largely remained elusive. Here, we integrated multi-omics data from a tractable organoid system with a metabolic modeling approach to uncover the metabolic and regulatory idiosyncrasies of the MRD. We find that the resistant cells, despite their non-proliferative phenotype and the absence of oncogenic signaling, feature increased glycolysis and activity of certain urea cycle enzyme reminiscent of the tumor. This metabolic distinctiveness was also evident in a mouse model and in transcriptomic data from patients following neo-adjuvant therapy. We further identified a marked similarity in DNA methylation profiles between tumor and residual cells. Taken together, our data reveal a metabolic and epigenetic memory of the treatment-resistant cells. We further demonstrate that the memorized elevated glycolysis in MRD is crucial for their survival and can be targeted using a small-molecule inhibitor without impacting normal cells. The metabolic aberrances of MRD thus offer new therapeutic opportunities for post-treatment care to prevent breast tumor recurrence. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Nature Research | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Metabolic memory underlying minimal residual disease in breast cancer | en_US |
dc.title.alternative | Metabolic memory underlying minimal residual disease in breast cancer | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
dc.source.pagenumber | 20 | en_US |
dc.source.volume | 17 | en_US |
dc.source.journal | Molecular Systems Biology | en_US |
dc.identifier.doi | 10.15252/msb.202010141 | |
dc.identifier.cristin | 1953014 | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |