Mitochondrial HER2 stimulates respiration and promotes tumorigenicity
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F24%3A00585963" target="_blank" >RIV/86652036:_____/24:00585963 - isvavai.cz</a>
Alternative codes found
RIV/67985823:_____/24:00585963 RIV/68378050:_____/24:00585963 RIV/00216208:11110/24:10480392 RIV/00216208:11310/24:10480392
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/10.1111/eci.14174" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1111/eci.14174</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/eci.14174" target="_blank" >10.1111/eci.14174</a>
Alternative languages
Result language
angličtina
Original language name
Mitochondrial HER2 stimulates respiration and promotes tumorigenicity
Original language description
Background: Amplification of HER2, a receptor tyrosine kinase and a breast cancer-linked oncogene, is associated with aggressive disease. HER2 protein is localised mostly at the cell membrane, but a fraction translocates to mitochondria. Whether and how mitochondrial HER2 contributes to tumorigenicity is currently unknown. Methods: We enriched the mitochondrial (mt-)HER2 fraction in breast cancer cells using an N-terminal mitochondrial targeting sequence and analysed how this manipulation impacts bioenergetics and tumorigenic properties. The role of the tyrosine kinase activity of mt-HER2 was assessed in wild type, kinase-dead (K753M) and kinase-enhanced (V659E) mtHER2 constructs. Results: We document that mt-HER2 associates with the oxidative phosphorylation system, stimulates bioenergetics and promotes larger respiratory supercomplexes. mt-HER2 enhances proliferation and invasiveness in vitro and tumour growth and metastatic potential in vivo, in a kinase activity-dependent manner. On the other hand, constitutively active mt-HER2 provokes excessive mitochondria ROS generation, sensitises to cell death, and restricts growth of primary tumours, suggesting that regulation of HER2 activity in mitochondria is required for the maximal pro-tumorigenic effect. Conclusions: mt-HER2 promotes tumorigenicity by supporting bioenergetics and optimal redox balance.
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
10601 - Cell 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
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
European Journal of Clinical Investigation
ISSN
0014-2972
e-ISSN
1365-2362
Volume of the periodical
54
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
e14174
UT code for WoS article
001154005800001
EID of the result in the Scopus database
2-s2.0-85183936702