Gkountela S Castro-Giner F Szczerba BM Vetter M Landin J Scherrer R Krol I Scheidmann MC Beisel C Stirnimann CU Kurzeder C Heinzelmann-Schwarz V Rochlitz C Weber WP Aceto N 2019 The ability of circulating tumor cells (CTCs) to form clusters has been linked to increased metastatic potential. Yet biological features and vulnerabilities of CTC clusters remain largely unknown. Here, we profile the DNA methylation landscape of single CTCs and CTC clusters from breast cancer patients and mouse models on a genome-wide scale. We find that binding sites for stemness- and proliferation-associated transcription factors are specifically hypomethylated in CTC clusters, including binding sites for OCT4, NANOG, SOX2, and SIN3A, paralleling embryonic stem cell biology. Among 2,486 FDA-approved compounds, we identify Na+/K+ ATPase inhibitors that enable the dissociation of CTC clusters into single cells, leading to DNA methylation remodeling at critical sites and metastasis suppression. Thus, our results link CTC clustering to specific changes in DNA methylation that promote stemness and metastasis and point to cluster-targeting compounds to suppress the spread of cancer. application/pdf https://sonar.ch/global/documents/60448 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2018.11.046 info:eu-repo/semantics/altIdentifier/pmid/30633912 info:eu-repo/semantics/openAccess Cell. - 2019 RNA sequencing bisulfite sequencing circulating tumor cell clusters circulating tumor cells drug screen proliferation-associated transcription factors single cell sequencing stemness-associated transcription factors Animals Breast Neoplasms Cell Differentiation Cell Line, Tumor Cell Proliferation DNA Methylation Disease Models, Animal Female Humans Mice Mice, Inbred NOD Nanog Homeobox Protein Neoplasm Metastasis Neoplastic Cells, Circulating Octamer Transcription Factor-3 Repressor Proteins SOXB1 Transcription Factors Circulating Tumor Cell Clustering Shapes DNA Methylation to Enable Metastasis Seeding. http://purl.org/coar/resource_type/c_6501