Nutrient requirements of organ-specific metastasis in breast cancer
Cancer metastasis is a major contributor to patient morbidity and mortality<sup>1</sup>, yet the factors that determine the organs where cancers can metastasize are incompletely understood. Here we quantify the absolute levels of 124 metabolites in multiple tissues in mice and investigate how this relates to the ability of breast cancer cells to grow in different organs. We engineered breast cancer cells with broad metastatic potential to be auxotrophic for specific nutrients and assessed their ability to colonize different tissue sites. We then asked how tumour growth in different tissues relates to nutrient availability and tumour biosynthetic activity. We find that single nutrients alone do not define the sites where breast cancer cells can grow as metastases. In addition, we identify purine synthesis as a requirement for tumour growth and metastasis across many tissues and find that this phenotype is independent of tissue nucleotide availability or tumour de novo nucleotide synthesis activity. These data suggest that a complex interplay between multiple nutrients within the microenvironment dictates potential sites of metastatic cancer growth, and highlights the interdependence between extrinsic environmental factors and intrinsic cellular properties in influencing where breast cancer cells can grow as metastases.
Authors
- Sharanya Sivanand (ORCID: https://orcid.org/0000-0002-2559-9270)
- Matthew G. Vander Heiden (ORCID: https://orcid.org/0000-0002-6702-4192)
- T. Brian (ORCID: https://orcid.org/0000-0003-4992-2623)
- S Trojan (ORCID: https://orcid.org/0000-0001-8876-6294)
- Rakesh K. Jain (ORCID: https://orcid.org/0000-0001-7571-3548)
- Keene L. Abbott (ORCID: https://orcid.org/0000-0002-6166-704X)
- Mayu Nakano
- Virginia Spanoudaki
- Tenzin Kunchok (ORCID: https://orcid.org/0000-0001-6603-4607)
- Anna M. Barbeau (ORCID: https://orcid.org/0000-0002-2382-4999)
- Mark Duquette
- Gino B. Ferraro (ORCID: https://orcid.org/0000-0002-1587-4259)
- Lisa Maria Riedmayr (ORCID: https://orcid.org/0000-0002-0307-2507)
- Florian Gourgue (ORCID: https://orcid.org/0000-0001-9777-806X)
- Ashwin S. Kumar (ORCID: https://orcid.org/0000-0003-3251-9977)
- Sophie Honeder (ORCID: https://orcid.org/0000-0002-7201-6293)
- Michelle Xiao Wu (ORCID: https://orcid.org/0000-0001-6894-7469)
- Yetiş Gültekin (ORCID: https://orcid.org/0000-0003-0103-351X)
- Xin Jin (ORCID: https://orcid.org/0000-0003-2344-992X)
- Nicole Henning
- Sophie Charlotte Steinbuch
- George M. Church
- Millenia Waite
- Diya Ramesh
- Muhammad Bin Munim
- Rafael Ferreira
- Anna Shevzov-Zebrun
- Kian Moritz Eghbalian
- Edrees H. Rashan
- P. H. Hansen (ORCID: https://orcid.org/0000-0002-6764-4789)
- Sonu Subudhi
- Francisco J. Sánchez-Rivera
- Ahmed Ali
Institutions
- Broad Institute (US)
- Jagiellonian University (PL)
- Harvard University (US)
- TU Wien (AT)
- Heidelberg University (DE)
- Westlake University (CN)
- Massachusetts General Hospital (US)
- Harvard–MIT Division of Health Sciences and Technology (US)
- Dana-Farber Cancer Institute (US)
- Dana-Farber/Harvard Cancer Center (US)
- Pediatrics and Genetics (US)
- Whitehead Institute for Biomedical Research (US)
- Massachusetts Institute of Technology (US)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Nature
- Published
- 2026-01-07
- DOI
- https://doi.org/10.1038/s41586-025-09898-9
- Citations
- 2
- Primary Topic
- Cancer Cells and Metastasis
- Type
- article
- Field-Weighted Citation Impact
- 48.39