Considerable evidence suggests breast cancer metastasis arises from cells undergoing epithelial-to-mesenchymal-transition (EMT) and cancer stem-like cells (CSCs). Using a microfluidic device that enriches migratory breast cancer cells with enhanced capacity for tumor formation and metastasis, we identified genes differentially expressed in migratory cells by high-throughput single-cell RNA-sequencing. Migratory cells exhibited overall signatures of EMT and CSCs with variable expression of marker genes, and they retained expression profiles of EMT over time. With single-cell resolution, we discovered intermediate EMT states and distinct epithelial and mesenchymal sub-populations of migratory cells, indicating breast cancer cells can migrate rapidly while retaining an epithelial state. Migratory cells showed differential profiles for regulators of oxidative stress, mitochondrial morphology, and the proteasome, revealing potential vulnerabilities and unexpected consequences of drugs. We also identified novel genes correlated with cell migration and outcomes in breast cancer as potential prognostic biomarkers and therapeutic targets to block migratory cells in metastasis.
Bibliographical noteFunding Information:
This work was supported by grants from National Institute of Health to E. Y. (R01 CA 203810 and R21 CA 195016). Y.-C. Chen acknowledges the support from University of Michigan Office of Research UMOR #26998 and Forbes Institute for Cancer Discovery. We thank the Lurie Nanofabrication Facility of the University of Michigan (Ann Arbor, MI) for device fabrication and Dr Jason Cong’s lab in UCLA for computation of sequencing read alignment.
© 2019 The Royal Society of Chemistry.
All Science Journal Classification (ASJC) codes
- Analytical Chemistry
- Environmental Chemistry