Docetaxel Inhibits Epithelial-Mesenchymal Transition in Human Mammary Cells

Samuel J. Beerkens, Jessica J. King, Kelly L. Irving, Sugandha Bhatia, Erik W. Thompson, Nicole M. Smith, K. Swaminathan Iyer, Cameron W. Evans

Research output: Contribution to journalArticlepeer-review

Abstract

Epithelial-mesenchymal transition (EMT) is a reversible and dynamic biological process in which epithelial cells acquire mesenchymal characteristics including enhanced stemness and migratory ability. EMT can facilitate cancer metastasis and is a known driver of cellular resistance to common chemotherapeutic drugs, such as docetaxel. Current chemotherapeutic practices such as docetaxel treatment can promote EMT and increase the chance of tumor recurrence and resistance, calling for new approaches in cancer treatment. Here we show that prolonged docetaxel treatment at a sub-IC50 concentration inhibits EMT in immortalized human mammary epithelial (HMLE) cells. Using immunofluorescence, flow cytometry, and bulk transcriptomic sequencing to assess EMT progression, we analyzed a range of cellular markers of EMT in docetaxel-treated cells and observed an upregulation of epithelial markers and downregulation of mesenchymal markers in the presence of docetaxel. This finding suggests that docetaxel may have clinical applications not only as a cytotoxic drug but also as an inhibitor of EMT-driven metastasis and multidrug resistance depending on the concentration of its use.

Original languageEnglish
Pages (from-to)53-61
Number of pages9
JournalMolecular Pharmaceutics
Volume21
Issue number1
Early online date29 Nov 2023
DOIs
Publication statusPublished - 1 Jan 2024

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