| Autor: |
Dugina V; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119991, Russia.; Biological Faculty, M.V. Lomonosov Moscow State University, Moscow 119991, Russia., Vasileva M; Scientific Research Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Moscow 115522, Russia., Khromova N; Scientific Research Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Moscow 115522, Russia., Vinokurova S; Scientific Research Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Moscow 115522, Russia., Shagieva G; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119991, Russia., Mikheeva E; Department of Pathology, Kazan State Medical University, Kazan 420012, Russia., Galembikova A; Department of Pathology, Kazan State Medical University, Kazan 420012, Russia., Dunaev P; Department of Pathology, Kazan State Medical University, Kazan 420012, Russia., Kudlay D; Department of Pharmacology, The I. M. Sechenov First Moscow State Medical University (The Sechenov University), Moscow 119991, Russia.; Department of Pharmacognosy and Industrial Pharmacy, Lomonosov Moscow State University, Moscow 119992, Russia., Boichuk S; Department of Pathology, Kazan State Medical University, Kazan 420012, Russia.; Department of Radiotherapy and Radiology, Russian Medical Academy of Continuous Professional Education, Moscow 119454, Russia.; 'Biomarker' Research Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia., Kopnin P; Scientific Research Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Moscow 115522, Russia. |
| Abstrakt: |
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. |
