Deciphering Pre-existing and Induced 3D Genome Architecture Changes involved in Constricted Melanoma Migration (Hi-C)

Metastatic cancer cells traverse tight junctions that exert forces on their nucleus and the genomic contents within. Cancerous tumors are highly heterogeneous and not all cells within them can achieve such a feat. Here, we investigated what initial genome architecture characteristics favor the constricted migratory ability of cancer cells and which arise only after passage through multiple constrictions. We identified a cell surface protein (ITGB4) whose expression correlates with increased initial constricted migration ability in human melanoma A375 cells. Sorting out this subpopulation allowed us to identify cellular and nuclear features that pre-exist and favor migration, as well as alterations that only appear after cells have passed through constrictions. We identified specific genomic regions that experienced altered genome spatial compartment profiles only after constricted migration. Our study reveals 3D genome structure contributions to both selection and induction mechanisms of cell fate change during cancer metastasis. A375 cells from either the original cell line population (Parental) or a population grown from a single cell (Clone3) were FACS sorted according to expression of Integrin Beta 4 (ITGB4). Cells were then allowed to migrate through 5 rounds of constricted migration. Genome structure was characterized by Hi-C across all populations and migration conditions.