Figure 1. Transcriptional heterogeneity and evolution of metastatic breast cancer.

Human breast cancer cells exhibit substantial intratumoral heterogeneity of EMP states. Within a given breast cancer subtype, more highly metastatic primary tumors are more likely to contain a larger proportion of mesenchymal-like cells compared with lowly metastatic tumors. Upon metastasis to the lung, the EMP profile of the primary tumor is retained. Transcriptional evolution during metastasis, instead of involving changes in the EMP profile, is characterized by upregulation of stress response genes in highly metastatic primary tumors, or of motility genes in lowly metastatic primary tumors.