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Title

Functional Pro-metastatic Heterogeneity Revealed by Spiked-scRNAseq Is Shaped by Cancer Cell Interactions and Restricted by VSIG1

Authors
Published in Cell Reports. 2020, vol. 33, no. 6, 108372
Abstract How cells with metastatic potential, or pro-metastatic states, arise within heterogeneous primary tumors remains unclear. Here, we have used one index primary colon cancer to develop spiked-scRNAseq to link omics-defined single-cell clusters with cell behavior. Using spiked-scRNAseq we uncover cell populations with differential metastatic potential in which pro-metastatic states are correlated with the expression of signaling and vesicle-trafficking genes. Analyzing such heterogeneity, we define an anti-metastatic, non-cell-autonomous interaction originating from non-/low-metastatic cells, and identify membrane VSIG1 as a critical mediator of this interaction. VSIG1 acts to restrict the development of pro-metastatic states autonomously and non-cell autonomously, in part by inhibiting YAP/TAZ-TEAD signaling. As VSIG1 re-expression is able to reduce metastatic behavior from multiple colon cancer cell types, the regulation of VSIG1 or its effectors opens new interventional opportunities. In general, we propose that crosstalk between cancer cells, including the action of VSIG1, dynamically defines the degree of pro-metastatic intra-tumoral heterogeneity.
Keywords VSIG1Cell interactionsClustersMetastasisMetastatic repressorNon-cell-autonomousPhenotype/expressed genotypePro-metastatic statesScRNAseqSingle cell.
Identifiers
PMID: 33176137
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Research group Stemness dans le développement et les maladies: Signalisation, reprogrammation et mécanismes des métastases (776)
Project
Swiss National Science Foundation: 31003A_177340
Citation
(ISO format)
BERNAL ZAMORA, Carolina et al. Functional Pro-metastatic Heterogeneity Revealed by Spiked-scRNAseq Is Shaped by Cancer Cell Interactions and Restricted by VSIG1. In: Cell Reports, 2020, vol. 33, n° 6, p. 108372. doi: 10.1016/j.celrep.2020.108372 https://archive-ouverte.unige.ch/unige:144923

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Deposited on : 2020-11-18

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