Mitochondrial HER2 stimulates respiration and promotes tumorigenicity

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/67985823:_____/24:00585963 RIV/68378050:_____/24:00585963 RIV/00216208:11110/24:10480392 RIV/00216208:11310/24:10480392

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Mitochondrial HER2 stimulates respiration and promotes tumorigenicity

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Mitochondrial HER2 stimulates respiration and promotes tumorigenicity

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Clinical Investigation

ISSN

0014-2972

e-ISSN

1365-2362

Svazek periodika

54

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

e14174

Kód UT WoS článku

001154005800001

EID výsledku v databázi Scopus

2-s2.0-85183936702