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Issue 24, 2019
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Single-cell RNA-sequencing of migratory breast cancer cells: discovering genes associated with cancer metastasis

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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.

Graphical abstract: Single-cell RNA-sequencing of migratory breast cancer cells: discovering genes associated with cancer metastasis

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Supplementary files

Article information


Submitted
18 Jul 2019
Accepted
02 Nov 2019
First published
04 Nov 2019

Analyst, 2019,144, 7296-7309
Article type
Paper

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

Y. Chen, S. Sahoo, R. Brien, S. Jung, B. Humphries, W. Lee, Y. Cheng, Z. Zhang, K. E. Luker, M. S. Wicha, G. D. Luker and E. Yoon, Analyst, 2019, 144, 7296
DOI: 10.1039/C9AN01358J

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