EGFR inhibition reverses epithelial‑mesenchymal transition, and decreases tamoxifen resistance via Snail and Twist downregulation in breast cancer cells.

Abstract	Tamoxifen resistance remains a major obstacle in the treatment of estrogen receptor (ER)‑positive breast cancer. In recent years, the crucial role of the epithelial‑mesenchymal transition (EMT) process in the development of drug resistance in breast cancer has been underlined. However, the central molecules inducing the EMT process during the development of tamoxifen resistance remain to be elucidated. In the present study, it was demonstrated that tamoxifen‑resistant breast cancer cells underwent EMT and exhibited an enhanced cell motility and invasive behavior. The inhibition of snail family transcriptional repressor 1 (Snail) and twist family BHLH transcription factor 1 (Twist) reversed the EMT phenotype and decreased the tamoxifen resistance, migration and invasion of tamoxifen‑resistant breast cancer cells. In addition, it was observed that the inhibition of epidermal growth factor receptor (EGFR) reversed the EMT phenotype in tamoxifen‑resistant MCF7 (MCF‑7/TR) cells via the downregulation of Snail and Twist. Notably, the EGFR inhibitor, gefitinib, decreased tamoxifen resistance, migration and invasion through the inhibition of Snail and Twist. On the whole, the results of the present study suggest that EGFR may be a promising therapeutic target for tamoxifen‑resistant breast cancer. Moreover, it was suggested that gefitinib may serve as a potent novel therapeutic strategy for breast cancer patients, who have developed tamoxifen resistance.
Authors	Tomoya Takeda, Masanobu Tsubaki, Takuya Matsuda, Akihiro Kimura, Minami Jinushi, Teruki Obana, Manabu Takegami, Shozo Nishida
Journal	Oncology reports (Oncol Rep) Vol. 47 Issue 6 (Jun 2022) ISSN: 1791-2431 [Electronic] Greece
PMID	35445730 (Publication Type: Journal Article)
Chemical References	Tamoxifen EGFR protein, human ErbB Receptors Gefitinib
Topics	Breast Neoplasms (drug therapy, genetics, metabolism) Cell Line, Tumor Down-Regulation Drug Resistance, Neoplasm (genetics) Epithelial-Mesenchymal Transition ErbB Receptors (genetics, metabolism) Female Gefitinib (therapeutic use) Humans Tamoxifen (pharmacology, therapeutic use)

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