Migration speed of captured breast cancer subpopulations correlates with metastatic fitness

The genetic alterations contributing to migration proficiency, a phenotypic hallmark of metastatic cells required for colonizing distant organs, remain poorly defined. Here, we used single-cell magneto-optical capture (scMOCa) to isolate fast cells from heterogeneous breast cancer cell populations, based on their migratory ability alone. We show that captured fast cell subpopulations retain higher migration speed and focal adhesion dynamics over many generations due to a motility-related transcriptomic profile. Upregulated genes in fast selected cells encoded integrin subunits, proto-cadherins and numerous other genes associated with cell migration. Dysregulation of several of these genes correlated with poor survival outcomes in patients, while primary tumors established from fast cells generated a higher number of circulating tumor cells and soft tissue metastases in vivo. Subpopulations of cells selected for a highly migratory phenotype demonstrated an increased fitness for metastasis. We compare parental cells to captured cells. We have 2 batches of 3 technical replicates for the 2 biological replicates. 12 samples in total.