Heterogeneity in 2,6-Linked Sialic Acids Potentiates Invasion of Breast Cancer Epithelia

Heterogeneity in phenotypes of malignantly transformed cells and aberrant glycan expression on their surface are two prominent hallmarks cancers that have hitherto not been linked to each other. In this paper, we identify differential levels a specific linkage: ?2,6-linked sialic acids within breast cancer vivo culture. Upon sorting out populations with moderate, relatively higher, cell acid from the triple-negative line MDA-MB-231, both (denoted as medium high 2,6-Sial cells, respectively) stably retained early passages. continuous culturing, recapitulated heterogeneity unsorted whereas showed no such tendency. Compared counterparts greater adhesion reconstituted extracellular matrices (ECMs) invaded faster single cells. The level sublines was found be consistent glycosyl transferase, ST6GAL1. Stably knocking down ST6GAL1 enhanced invasiveness. When cultured together, differentially migrated edge growing tumoroid-like cocultures, formed central bulk. Multiscale simulations Cellular Potts model-based computational environment calibrated our experimental findings suggest cell–ECM adhesion, likely regulated by acids, facilitate niches highly invasive efficiently migrate centrifugally front malignant tumor.