Buchumschlag

Metabolic memory underlying minimal residual disease in breast cancer

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Radić Shechter, Ksenija (VerfasserIn) , Kafkia, Eleni (VerfasserIn) , Zirngibl, Katharina (VerfasserIn) , Gawrzak, Sylwia (VerfasserIn) , Alladin, Ashna (VerfasserIn) , Machado, Daniel (VerfasserIn) , Lüchtenborg, Christian (VerfasserIn) , Sévin, Daniel Charles (VerfasserIn) , Brügger, Britta (VerfasserIn) , Patil, Kiran Raosaheb (VerfasserIn) , Jechlinger, Martin (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 29 September 2021
In: Molecular systems biology
Year: 2021, Jahrgang: 17, Heft: 10, Pages: 1-21
ISSN:1744-4292
DOI:10.15252/msb.202010141
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/msb.202010141
Verlag, lizenzpflichtig, Volltext: https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=DOISource&SrcApp=WOS&KeyAID=10.15252%2Fmsb.202010141&DestApp=DOI&SrcAppSID=C3vor5GMCJilxsEqfPX&SrcJTitle=MOLECULAR+SYSTEMS+BIOLOGY&DestDOIRegistrantName=EMBO
Volltext
Verfasserangaben:Ksenija Radic Shechter, Eleni Kafkia, Katharina Zirngibl, Sylwia Gawrzak, Ashna Alladin, Daniel Machado, Christian Luechtenborg, Daniel C. Sevin, Britta Bruegger, Kiran R. Patil and Martin Jechlinger
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 28.01.2022
Beschreibung:Online Resource
ISSN:1744-4292
DOI:10.15252/msb.202010141

Ähnliche Einträge