Selective Disruption of Respiratory Supercomplexes as a New Strategy to Suppress Her2^high Breast Cancer.

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 Her2^high disease.

Results

We demonstrate that Her2^high 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 Her2^high tumors without systemic toxicity. Mechanistically, MitoTam inhibits complex I-driven respiration and disrupts respiratory SCs in Her

SUBMITTER: Rohlenova K 

PROVIDER: S-EPMC5206771 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature