Reduced ER-mitochondria connectivity promotes neuroblastoma multidrug resistance
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F22%3A00077600" target="_blank" >RIV/00159816:_____/22:00077600 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/22:00125550
Result on the web
<a href="https://www.embopress.org/doi/full/10.15252/embj.2021108272" target="_blank" >https://www.embopress.org/doi/full/10.15252/embj.2021108272</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.15252/embj.2021108272" target="_blank" >10.15252/embj.2021108272</a>
Alternative languages
Result language
angličtina
Original language name
Reduced ER-mitochondria connectivity promotes neuroblastoma multidrug resistance
Original language description
Most cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptosis. Mitochondria isolated from neuroblastoma cells were exposed to tBid or Bim, death effectors activated by therapeutic stress. Multidrug-resistant tumor cells obtained from children at relapse had markedly attenuated Bak and Bax oligomerization and cytochrome c release (surrogates for apoptotic commitment) in comparison with patient-matched tumor cells obtained at diagnosis. Electron microscopy identified reduced ER-mitochondria-associated membranes (MAMs; ER-mitochondria contacts, ERMCs) in therapy-resistant cells, and genetically or biochemically reducing MAMs in therapy-sensitive tumors phenocopied resistance. MAMs serve as platforms to transfer Ca2+ and bioactive lipids to mitochondria. Reduced Ca2+ transfer was found in some but not all resistant cells, and inhibiting transfer did not attenuate apoptotic signaling. In contrast, reduced ceramide synthesis and transfer was common to resistant cells and its inhibition induced stress resistance. We identify ER-mitochondria-associated membranes as physiologic regulators of apoptosis via ceramide transfer and uncover a previously unrecognized mechanism for cancer multidrug 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
<a href="/en/project/GJ20-00987Y" target="_blank" >GJ20-00987Y: Mitochondrial dynamics and autophagy: A missing link between dedifferentiation and development of resistance in pediatric solid tumors</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Embo Journal
ISSN
0261-4189
e-ISSN
1460-2075
Volume of the periodical
41
Issue of the periodical within the volume
8
Country of publishing house
US - UNITED STATES
Number of pages
20
Pages from-to
nestrankovano
UT code for WoS article
000760798100001
EID of the result in the Scopus database
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