Mitochondrial fragmentation, elevated mitochondrial superoxide and respiratory supercomplexes disassembly is connected with the tamoxifen-resistant phenotype of breast cancer cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F19%3A00520490" target="_blank" >RIV/86652036:_____/19:00520490 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0891584919310044?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0891584919310044?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.freeradbiomed.2019.09.004" target="_blank" >10.1016/j.freeradbiomed.2019.09.004</a>
Alternative languages
Result language
angličtina
Original language name
Mitochondrial fragmentation, elevated mitochondrial superoxide and respiratory supercomplexes disassembly is connected with the tamoxifen-resistant phenotype of breast cancer cells
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Free Radical Biology and Medicine
ISSN
0891-5849
e-ISSN
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Volume of the periodical
143
Issue of the periodical within the volume
NOV 1 2019
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
510-521
UT code for WoS article
000496132900047
EID of the result in the Scopus database
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