Number of the records: 1
Mitochondrial fragmentation, elevated mitochondrial superoxide and respiratory supercomplexes disassembly is connected with the tamoxifen-resistant phenotype of breast cancer cells
- 1.
SYSNO ASEP 0520490 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Mitochondrial fragmentation, elevated mitochondrial superoxide and respiratory supercomplexes disassembly is connected with the tamoxifen-resistant phenotype of breast cancer cells Author(s) Tomkova, Veronika (BTO-N)
Sandoval-Acuna, Cristian (BTO-N)
Torrealba, Natalia (BTO-N)
Truksa, Jaroslav (BTO-N) RID, ORCIDNumber of authors 4 Source Title Free Radical Biology and Medicine. - : Elsevier - ISSN 0891-5849
Roč. 143, NOV 1 2019 (2019), s. 510-521Number of pages 12 s. Language eng - English Country US - United States Keywords activated protein-kinase ; estrogen-receptor-alpha ; acquired-resistance ; Mitochondrial fragmentation ; Reactive oxygen species Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology R&D Projects GA16-12816S GA ČR - Czech Science Foundation (CSF) GA18-13103S GA ČR - Czech Science Foundation (CSF) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support BTO-N - RVO:86652036 UT WOS 000496132900047 DOI 10.1016/j.freeradbiomed.2019.09.004 Annotation Tamoxifen resistance remains a clinical obstacle in the treatment of hormone sensitive breast cancer. It has been reported that tamoxifen is able to target respiratory complex I within mitochondria. Therefore, we established two tamoxifen-resistant cell lines, MCF7 Tam5R and T47D Tam5R resistant to 5 mu M tamoxifen and investigated whether tamoxifen-resistant cells exhibit mitochondrial changes which could help them survive the treatment. The function of mitochondria in this experimental model was evaluated in detail by studying i) the composition and activity of mitochondrial respiratory complexes, ii) respiration and glycolytic status, iii) mitochondrial distribution, dynamics and reactive oxygen species production. We show that Tam5R cells exhibit a significant decrease in mitochondrial respiration, low abundance of assembled mitochondrial respiratory supercomplexes, a more fragmented mitochondrial network connected with DRP1 Ser637 phosphorylation, higher glycolysis and sensitivity to 2-deoxyglucose. Tam5R cells also produce significantly higher levels of mitochondrial superoxide but at the same time increase their antioxidant defense (CAT, SOD2) through upregulation of SIRT3 and show phosphorylation of AMPK at Ser 485/491. Importantly, MCF7 rho 0 cells lacking functional mitochondria exhibit a markedly higher resistance to tamoxifen, supporting the role of mitochondria in tamoxifen resistance. We propose that reduced mitochondrial function and higher level of reactive oxygen species within mitochondria in concert with metabolic adaptations contribute to the phenotype of tamoxifen resistance. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2020 Electronic address https://www.sciencedirect.com/science/article/pii/S0891584919310044?via%3Dihub
Number of the records: 1