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

Article Article scientifique Article Functional Pro-metastatic Heterogeneity Revealed by Spiked-scRNAseq Is Shaped by Cancer Cell Interactions and Restricted by VSIG1 eng 2020 author Bernal Zamora Carolina 797742 author Silvano Marianna 859998 author Tapponnier Yann 892698 author Anand Santosh 856950 author Angulo Valdivia Cecilia 832386 author Ruiz Altaba Ariel 135639 108372 10.1016/j.celrep.2020.108372 33176137 2211-1247 https://linkinghub.elsevier.com/retrieve/pii/S2211124720313619 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. VSIG1 Cell interactions Clusters Metastasis Metastatic repressor Non-cell-autonomous Phenotype/expressed genotype Pro-metastatic states ScRNAseq Single cell Dewey 576.5 Swiss National Science Foundation Mechanisms establishing a pro-metastatic state 177340 CH Project funding 135 Département de médecine génétique et développement 21D false 446 Stemness dans le développement et les maladies: Signalisation, reprogrammation et mécanismes des métastases 776 Cell Reports 33 6 13646a78-9494-4bd0-9506-01a52fe3b069 Article (Published version) Public 1-s2.0-S2211124720313619-mmc2.pdf 22598507 application/pdf CC BY-NC-ND Vignette Public Vignette.jpg 55995 image/jpeg openAccess Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement

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Functional Pro-metastatic Heterogeneity Revealed by Spiked-scRNAseq Is Shaped by Cancer Cell Interactions and Restricted by VSIG1	Cell Reports			2020	311	130

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Tapponnier, Yann