Imbalance between Actin Isoforms Contributes to Tumour Progression in Taxol-Resistant Triple-Negative Breast Cancer Cells

• Published in: International journal of molecular sciences Vol. 25; no. 8; p. 4530
• Main Authors: Dugina, Vera, Vasileva, Maria, Khromova, Natalia, Vinokurova, Svetlana, Shagieva, Galina, Mikheeva, Ekaterina, Galembikova, Aigul, Dunaev, Pavel, Kudlay, Dmitry, Boichuk, Sergei, Kopnin, Pavel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20-04-2024
• Subjects: actin isoforms; Actins - metabolism; Animals; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents, Phytogenic - pharmacology; Breast cancer; Cell culture; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Development and progression; Disease Progression; Drug resistance; Drug Resistance, Neoplasm; EMT; Epithelial-Mesenchymal Transition - drug effects; Female; Gene Expression Regulation, Neoplastic - drug effects; Genotype & phenotype; Humans; Metastasis; Mice; Microscopy; microtubule reorganisation; Muscle proteins; Paclitaxel - pharmacology; Pore size; pro-metastatic changes; Protein Isoforms - metabolism; Proteins; Scientific equipment and supplies industry; Stem cells; taxol resistance; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; Tubulins; Tumors; United States; California; Russia; microtubule reorganisation; taxol resistance; breast cancer; actin isoforms; pro-metastatic changes; EMT
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25084530

The widespread occurrence of breast cancer and its propensity to develop drug resistance highlight the need for a comprehensive understanding of the molecular mechanisms involved. This study investigates the intricate pathways associated with secondary resistance to taxol in triple-negative breast cancer (TNBC) cells, with a particular focus on the changes observed in the cytoplasmic actin isoforms. By studying a taxol-resistant TNBC cell line, we revealed a shift between actin isoforms towards γ-actin predominance, accompanied by increased motility and invasive properties. This was associated with altered tubulin isotype expression and reorganisation of the microtubule system. In addition, we have shown that taxol-resistant TNBC cells underwent epithelial-to-mesenchymal transition (EMT), as evidenced by Twist1-mediated downregulation of E-cadherin expression and increased nuclear translocation of β-catenin. The RNA profiling analysis revealed that taxol-resistant cells exhibited significantly increased positive regulation of cell migration, hormone response, cell-substrate adhesion, and actin filament-based processes compared with naïve TNBC cells. Notably, taxol-resistant cells exhibited a reduced proliferation rate, which was associated with an increased invasiveness in vitro and in vivo, revealing a complex interplay between proliferative and metastatic potential. This study suggests that prolonged exposure to taxol and acquisition of taxol resistance may lead to pro-metastatic changes in the TNBC cell line.