biostudies-literatureYoon SBBrenda Nease Breast Cancer FundEmory UniversityNational Cancer InstituteNCI NIH HHSNational Institutes of HealthNIGMS NIH HHSNIH HHSWinship Cancer Institutee202308080https://www.ebi.ac.uk/biostudies/studies/S-EPMC10982113biostudies-literatureUnknown223(6)Phenotypic heterogeneity poses a significant hurdle for cancer treatment but is under-characterized in the context of tumor invasion. Amidst the range of phenotypic heterogeneity across solid tumor types, collectively invading cells and single cells have been extensively characterized as independent modes of invasion, but their intercellular interactions have rarely been explored. Here, we isolated collectively invading cells and single cells from the heterogeneous 4T1 cell line and observed extensive transcriptional and epigenetic diversity across these subpopulations. By integrating these datasets, we identified laminin-332 as a protein complex exclusively secreted by collectively invading cells. Live-cell imaging revealed that laminin-332 derived from collectively invading cells increasThe Journal of cell biologySubpopulation commensalism promotes Rac1-dependent invasion of single cells via laminin-332.PMC10982113P01 CA257906R01 CA250422PO1CA257906R50 CA265345R01CA236369R01CA250422R01 CA236369P30 CA138292P30CA138292R01 CA247367R01CA247367R50CA265345T32 GM145735Robinson IEMarcus AIChen LKhatib TOYoon SBArthur RAMouw JKClaussen HZohbi NMWu HfalseSubpopulation commensalism promotes Rac1-dependent invasion of single cells via laminin-332.Phenotypic heterogeneity poses a significant hurdle for cancer treatment but is under-characterized in the context of tumor invasion. Amidst the range of phenotypic heterogeneity across solid tumor types, collectively invading cells and single cells have been extensively characterized as independent modes of invasion, but their intercellular interactions have rarely been explored. Here, we isolated collectively invading cells and single cells from the heterogeneous 4T1 cell line and observed extensive transcriptional and epigenetic diversity across these subpopulations. By integrating these datasets, we identified laminin-332 as a protein complex exclusively secreted by collectively invading cells. Live-cell imaging revealed that laminin-332 derived from collectively invading cells increas2024-01-01T00:00:00Z2024 Jun2026-06-03T07:14:43.426Z2025-04-06T09:33:51.378ZS-EPMC109821133855149710.1083/jcb.202308080