Single-cell lineages reveal the rates, routes, and drivers of metastasis in cancer xenografts
Top Cited Papers
- 26 February 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 371 (6532), 909-+
- https://doi.org/10.1126/science.abc1944
Abstract
Detailed phylogenies of tumor populations can recount the history and chronology of critical events during cancer progression, such as metastatic dissemination. We applied a Cas9-based, single-cell lineage tracer to study the rates, routes, and drivers of metastasis in a lung cancer xenograft mouse model. We report deeply resolved phylogenies for tens of thousands of cancer cells traced over months of growth and dissemination. This revealed stark heterogeneity in metastatic capacity, arising from pre-existing and heritable differences in gene expression. We demonstrate that these identified genes can drive invasiveness, and uncovered an unanticipated suppressive role for KRT17. We also show that metastases disseminated via multidirectional tissue routes and complex seeding topologies. Overall, we demonstrate the power of tracing cancer progression at subclonal resolution and vast scale.Keywords
Funding Information
- National Institutes of Health (1RM1 HG009490-01)
- National Institutes of Health (R01CA231300)
- National Institutes of Health (U54CA224081)
- National Institutes of Health (R01CA204302)
- National Institutes of Health (R01CA211052)
- National Institutes of Health (R01CA169338)
- National Institutes of Health (U01 CA217882-01)
- Howard Hughes Medical Institute
- National Institute of Allergy and Infectious Diseases (U19 AI090023)
- Pew Charitable Trusts
- Alexander and Margaret Stewart Trust
- Howard Hughes Medical Institute
- Chan Zuckerberg Initiative (2018-184034)
- National Institute of General Medical Sciences (GM125247)
- University of California, San Francisco Discovery Fellowship
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