Epithelial–Mesenchymal Transition of Breast Cancer Cells Induced by Activation of the Transcription Factor Snail1

---

Nikita I. Litovka^1#, Irina Y. Zhitnyak^1#, and Natalya A. Gloushankova^1,a*

¹N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia

^* To whom correspondence should be addressed.

^# These authors contributed equally to the study.

Received September 1, 2022; Revised October 27, 2022; Accepted November 11, 2022

---

Cancer cells use the program of epithelial–mesenchymal transition (EMT) for initiation of the invasion–metastasis cascade. Using confocal and video-microscopy, reorganization of the cytoskeleton was studied in the MCF-7 breast cancer cells undergoing Snail1-induced EMT. We used the line of MCF-7 cells stably expressing tetOff SNAI1 construct (MCF-7-SNAI1 cells). After tetracycline washout and Snail1 activation MCF-7-SNAI1 cells underwent EMT and acquired a migratory phenotype while retaining expression of E-cadherin. We identified five variants of the mesenchymal phenotype, differing in cell morphology and migration velocity. Migrating cells had high degree of plasticity, which allowed them to quickly change both the phenotype and migration velocity. The changes of the phenotype of MCF-7-SNAI1 cells are based on the Arp2/3-mediated branched actin network polymerization in lamellipodia, myosin-based contractility in the zone behind the nucleus, redistribution of adhesive proteins from cell–cell contacts to the leading edge, and reorganization of intermediate keratin filaments.

---

KEY WORDS: cancer cell, Snail1/SNAI1, epithelial–mesenchymal transition, cell migration, cancer cell plasticity, cell–cell adhesion, cytoskeleton, actin, myosin

DOI: 10.1134/S0006297923010030

---