Abstract
In this issue of Cell Stem Cell, Fumagalli et al. (2020) employ intravital microscopy of colorectal cancer organoid xenografts to investigate the cell of origin of metastases. While tumor-initiating cells are Lgr5(+), most disseminated cancer cells are Lgr5(-) and seed liver metastases in which Lgr5(+) cells then appear, showing that bidirectional plasticity of phenotypic states drives metastasis.