Triple negative breast tumors contain heterogeneous cancer cells expressing distinct KRAS-dependent collective and disseminative invasion programs

Inter-patient and intra-tumoral heterogeneity complicate the identification of predictive biomarkers and effective treatments for basal triple-negative breast cancer (b-TNBC). Invasion is the initiating event in metastasis and can occur by both collective and single-cell mechanisms. To identify molecular regulators driving these invasive phenotypes, the authors developed a workflow to isolate individual organoids from the collagen gels based on invasive morphology and perform RNA sequencing. The authors found that inhibition of EGFR, MAPK/ERK, or PI3K/AKT signaling reduced invasion. In addition, ERK inhibition was striking for its ability to inhibit collective invasion and dissemination effectively. The study concluded that different cancer cells in the same b-TNBC tumor could express different metastatic molecular programs and identified KRAS and ERK as essential regulators of collective and single-cell dissemination.