Single-cell RNA-sequencing of migratory breast cancer cells: Discovering genes associated with cancer metastasis

Yu Chih Chen, Saswat Sahoo, Riley Brien, Seungwon Jung, Brock Humphries, Woncheol Lee, Yu Heng Cheng, Zhixiong Zhang, Kathryn E. Luker, Max S. Wicha, Gary D. Luker, Euisik Yoon

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)7296-7309
Number of pages14
JournalAnalyst
Volume144
Issue number24
DOIs
Publication statusPublished - 2019 Dec 21

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry
  • Environmental Chemistry
  • Spectroscopy
  • Electrochemistry

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    Chen, Y. C., Sahoo, S., Brien, R., Jung, S., Humphries, B., Lee, W., Cheng, Y. H., Zhang, Z., Luker, K. E., Wicha, M. S., Luker, G. D., & Yoon, E. (2019). Single-cell RNA-sequencing of migratory breast cancer cells: Discovering genes associated with cancer metastasis. Analyst, 144(24), 7296-7309. https://doi.org/10.1039/c9an01358j