|Dataset type:||Expression profiling by high throughput sequencing|
|Number of samples:||210|
|Release date:||Jan 11 2019|
|Last update date:||Feb 18 2019|
|Dataset link||Circulating Tumor Cells Clustering Triggers DNA Methylation Changes to Enable Metastasis Seeding|
The ability of circulating tumor cells (CTCs) to form clusters is key to accelerate the metastatic process. Yet, biological features and vulnerabilities of CTC-clusters remain largely unknown. Here, we profile DNA methylation and RNA expression landscape of single CTCs and CTC-clusters, matched within individual breast cancer patients and mouse models. We find that clustering of CTC leads to a remarkable hypomethylation of binding sites for stemness-related transcription factors. Through a screen with 2’486 FDA-approved compounds, we identify drugs that are able to dissociate CTC-clusters into single cells, leading to DNA re-methylation at critical sites and to a reduction in metastasis-seeding ability. Thus, clustering of CTCs favors accessibility to binding sites of stemness-related transcription factors, and cluster-dissociating compounds enable to suppress the spread of cancer.