Journal article
Selective Disruption of Respiratory Supercomplexes as a New Strategy to Suppress Her2high Breast Cancer
K Rohlenova, K Sachaphibulkij, J Stursa, A Bezawork-Geleta, J Blecha, B Endaya, L Werner, J Cerny, R Zobalova, J Goodwin, T Spacek, E Alizadeh Pesdar, B Yan, MN Nguyen, M Vondrusova, M Sobol, P Jezek, P Hozak, J Truksa, J Rohlena Show all
Antioxidants and Redox Signaling | MARY ANN LIEBERT, INC | Published : 2017
Abstract
Aims: Expression of the HER2 oncogene in breast cancer is associated with resistance to treatment, and Her2 may regulate bioenergetics. Therefore, we investigated whether disruption of the electron transport chain (ETC) is a viable strategy to eliminate Her2high disease. Results: We demonstrate that Her2high cells and tumors have increased assembly of respiratory supercomplexes (SCs) and increased complex I-driven respiration in vitro and in vivo. They are also highly sensitive to MitoTam, a novel mitochondrial-Targeted derivative of tamoxifen. Unlike tamoxifen, MitoTam efficiently suppresses experimental Her2high tumors without systemic toxicity. Mechanistically, MitoTam inhibits complex I-..
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Awarded by Australian Research Council
Funding Acknowledgements
This research was supported in part by grants from the Australian Research Council (DP110105009) to J.N. and L.F.D., from the National and Health Medical Research Council of Australia (APP1011955), the Australian Research Council (DP130101651, DP15010280) the Cancer Council Queensland (APP1049104) to J.N., by the Czech Science Foundation grants to J.N. (16-12719S), J.R. (16-22823S) and J.T. (13-28830S and 16-12816S), by the Technology Agency of the Czech Republic (TE01020118), Ministry of Industry and Trade of the Czech Republic (FR-TI3/588), Institutional Research Support (RVO: 68378050) to M.S. and P.H., by the BIOCEV European Regional Development Fund CZ.1.05/1.100/02.0109 and the LQ1604 project of the National Sustainability Program II by the Ministry of Education, Youth and Sports.