Docetaxel Inhibits Epithelial-Mesenchymal Transition in Human Mammary Cells.
Samuel J BeerkensJessica J KingKelly L IrvingSugandha BhatiaErik W ThompsonNicole M SmithKillugudi Swaminathan IyerCameron W EvansPublished in: Molecular pharmaceutics (2023)
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-IC 50 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.
Keyphrases
- epithelial mesenchymal transition
- signaling pathway
- induced apoptosis
- transforming growth factor
- locally advanced
- cell cycle arrest
- endothelial cells
- stem cells
- flow cytometry
- bone marrow
- cell proliferation
- healthcare
- primary care
- squamous cell carcinoma
- endoplasmic reticulum stress
- single cell
- papillary thyroid
- rna seq
- induced pluripotent stem cells
- radiation therapy
- poor prognosis
- long non coding rna
- lymph node metastasis
- electronic health record