Rxivist logo

Single-cell lineages reveal the rates, routes, and drivers of metastasis in cancer xenografts

By Jeffrey J Quinn, Matthew G Jones, Ross A. Okimoto, Shigeki Nanjo, Michelle M. Chan, Nir Yosef, Trever G. Bivona, Jonathan S. Weissman

Posted 17 Apr 2020
bioRxiv DOI: 10.1101/2020.04.16.045245

Cancer progression is characterized by rare, transient events which are nonetheless highly consequential to disease etiology and mortality. Detailed cell phylogenies can recount the history and chronology of these critical events – including metastatic seeding. Here, we applied our Cas9-based lineage tracer to study the subclonal dynamics of metastasis in a lung cancer xenograft mouse model, revealing the underlying rates, routes, and drivers of metastasis. We report deeply resolved phylogenies for tens of thousands of metastatically disseminated cancer cells. We observe surprisingly diverse metastatic phenotypes, ranging from metastasis-incompetent to aggressive populations. These phenotypic distinctions result from pre-existing, heritable, and characteristic differences in gene expression, and we demonstrate that these differentially expressed genes can drive invasiveness. Furthermore, metastases transit via diverse, multidirectional tissue routes and seeding topologies. Our work demonstrates the power of tracing cancer progression at unprecedented resolution and scale. One Sentence Summary Single-cell lineage tracing and RNA-seq capture diverse metastatic behaviors and drivers in lung cancer xenografts in mice. ### Competing Interest Statement J.S.W. is an advisor and/or has equity in KSQ Therapeutics, Maze Therapeutics, Amgen, Tenaya, and 5 AM Ventures. T.G.B. is an advisor to Novartis, Astrazeneca, Revolution Medicines, Array, Springworks, Strategia, Relay, Jazz, Rain and receives research funding from Novartis and Revolution Medicines.

Download data

  • Downloaded 2,366 times
  • Download rankings, all-time:
    • Site-wide: 3,114 out of 100,621
    • In cancer biology: 70 out of 3,602
  • Year to date:
    • Site-wide: 651 out of 100,621
  • Since beginning of last month:
    • Site-wide: 604 out of 100,621

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News

  • 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
  • 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
  • 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
  • 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
  • 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
  • 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
  • 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
  • 22 Jan 2019: Nature just published an article about Rxivist and our data.
  • 13 Jan 2019: The Rxivist preprint is live!