Mitochondrial HER2 stimulates respiratory chain function and drives tumorigenicity of breast cancer cells
Author(s)
Novais, Silvia Magalhaes
Novotna, Eliska
Rohlenova, Katerina
Rohlena, Jakub
Neuzil, Jiri
Griffith University Author(s)
Year published
2019
Metadata
Show full item recordAbstract
Amplification of HER2/ERBB2, a breast cancer oncogene, leads to resistance to therapy and poor prognosis in breast cancer patients. HER2, a member of the EGFR protein family, normally localizes to the plasma membrane. Recently, a fraction of HER2 has been reported at the inner mitochondrial membrane, where it interacts with the respiratory chain. Now we show that overexpression of mitochondrial HER2 (mtHER2) stimulates respiratory chain function in breast cancer cells in a tyrosine kinase‐dependent manner. Moreover, overexpression of mtHER2 increases proliferation, migration and reactive oxygen species production. Interestingly, ...
View more >Amplification of HER2/ERBB2, a breast cancer oncogene, leads to resistance to therapy and poor prognosis in breast cancer patients. HER2, a member of the EGFR protein family, normally localizes to the plasma membrane. Recently, a fraction of HER2 has been reported at the inner mitochondrial membrane, where it interacts with the respiratory chain. Now we show that overexpression of mitochondrial HER2 (mtHER2) stimulates respiratory chain function in breast cancer cells in a tyrosine kinase‐dependent manner. Moreover, overexpression of mtHER2 increases proliferation, migration and reactive oxygen species production. Interestingly, mtHER2 makes the cells prone to treatment with mitochondria‐targeted tamoxifen (MitoTam), a new respiratory complex I inhibitor now in clinical trials. Therefore, mtHER2 affects both tumorigenicity and sensitivity to treatment by regulating mitochondrial bioenergetics and represents therefore a new treatment opportunity in HER2 high breast cancer.
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View more >Amplification of HER2/ERBB2, a breast cancer oncogene, leads to resistance to therapy and poor prognosis in breast cancer patients. HER2, a member of the EGFR protein family, normally localizes to the plasma membrane. Recently, a fraction of HER2 has been reported at the inner mitochondrial membrane, where it interacts with the respiratory chain. Now we show that overexpression of mitochondrial HER2 (mtHER2) stimulates respiratory chain function in breast cancer cells in a tyrosine kinase‐dependent manner. Moreover, overexpression of mtHER2 increases proliferation, migration and reactive oxygen species production. Interestingly, mtHER2 makes the cells prone to treatment with mitochondria‐targeted tamoxifen (MitoTam), a new respiratory complex I inhibitor now in clinical trials. Therefore, mtHER2 affects both tumorigenicity and sensitivity to treatment by regulating mitochondrial bioenergetics and represents therefore a new treatment opportunity in HER2 high breast cancer.
View less >
Conference Title
European Journal of Clinical Investigation
Volume
49
Issue
S1
Subject
Clinical sciences
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
Medicine, Research & Experimental
General & Internal Medicine