Genome-wide in vivo screen of circulating tumor cells identifies SLIT2 as a regulator of metastasis

Fan Xia, Yuan Ma, Kangfu Chen, Bill Duong, Sharif Ahmed, Randy Atwal, David Philpott, Troy Ketela, Jennifer Pantea, Sichun Lin, Stephane Angers*, Shana O. Kelley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Circulating tumor cells (CTCs) break free from primary tumors and travel through the circulation system to seed metastatic tumors, which are the major cause of death from cancer. The identification of the major genetic factors that enhance production and persistence of CTCs in the bloodstream at a whole genome level would enable more comprehensive molecular mechanisms of metastasis to be elucidated and the identification of novel therapeutic targets, but this remains a challenging task due to the heterogeneity and extreme rarity of CTCs. Here, we describe an in vivo genome-wide CRISPR knockout screen using CTCs directly isolated from a mouse xenograft. This screen elucidated SLIT2-a gene encoding a secreted protein acting as a cellular migration cue-as the most significantly represented gene knockout in the CTC population. SLIT2 knockout cells are highly metastatic with hypermigratory and mesenchymal phenotype, resulting in enhanced cancer progression in xenograft models.

Original languageEnglish (US)
Article numbereabo7792
JournalScience Advances
Volume8
Issue number35
DOIs
StatePublished - Sep 2022

ASJC Scopus subject areas

  • General

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