期刊
NATURE CANCER
卷 1, 期 7, 页码 692-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s43018-020-0082-y
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资金
- Cancer Research UK [C19767/A27145]
- Merck KGaA, Darmstadt, Germany
- Chan Zuckerberg Initiative
- HHMI International Scholar award
- European Research Council Consolidator Grant (ERC-COG) [724471-HemTree2.0]
- Wolfson Foundation and Family Charitable Trust
- Thompson Family Foundation [509044]
- Israel Science Foundation [703/15, 401/17, 1384/1]
- Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine
- Helen and Martin Kimmel award for innovative investigation
- NeuroMac DFG/Transregional Collaborative Research Center Grant, an International Progressive MS Alliance/NMSS [PA-1604 08459]
- Adelis Foundation
- European Research Council (ERC) [754320]
- Israel Cancer Research Fund
- Laura Gurwin Flug Family Fund
- Peter and Patricia Gruber Awards
- Comisaroff Family Trust
- Estate of Annice Anzelewitz
- Estate of Mordecai M. Roshwal
Tumors are supported by cancer-associated fibroblasts (CAFs). CAFs are heterogeneous and carry out distinct cancer-associated functions. Understanding the full repertoire of CAFs and their dynamic changes as tumors evolve could improve the precision of cancer treatment. Here we comprehensively analyze CAFs using index and transcriptional single-cell sorting at several time points along breast tumor progression in mice, uncovering distinct subpopulations. Notably, the transcriptional programs of these subpopulations change over time and in metastases, transitioning from an immunoregulatory program to wound-healing and antigen-presentation programs, indicating that CAFs and their functions are dynamic. Two main CAF subpopulations are also found in human breast tumors, where their ratio is associated with disease outcome across subtypes and is particularly correlated with BRCA mutations in triple-negative breast cancer. These findings indicate that the repertoire of CAF changes over time in breast cancer progression, with direct clinical implications. Scherz-Shouval and colleagues characterize the dynamic changes in cancer-associated fibroblast subpopulations during breast cancer progression. They find that the ratio of S100A4(+) and PDPN+ CAF subsets is associated with clinical outcome.
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