| First Author | Dufour CR | Year | 2022 |
| Journal | Commun Biol | Volume | 5 |
| Issue | 1 | Pages | 955 |
| PubMed ID | 36097051 | Mgi Jnum | J:329008 |
| Mgi Id | MGI:7339593 | Doi | 10.1038/s42003-022-03942-4 |
| Citation | Dufour CR, et al. (2022) Integrated multi-omics analysis of adverse cardiac remodeling and metabolic inflexibility upon ErbB2 and ERRalpha deficiency. Commun Biol 5(1):955 |
| abstractText | Functional oncogenic links between ErbB2 and ERRalpha in HER2+ breast cancer patients support a therapeutic benefit of co-targeted therapies. However, ErbB2 and ERRalpha also play key roles in heart physiology, and this approach could pose a potential liability to cardiovascular health. Herein, using integrated phosphoproteomic, transcriptomic and metabolic profiling, we uncovered molecular mechanisms associated with the adverse remodeling of cardiac functions in mice with combined attenuation of ErbB2 and ERRalpha activity. Genetic disruption of both effectors results in profound effects on cardiomyocyte architecture, inflammatory response and metabolism, the latter leading to a decrease in fatty acyl-carnitine species further increasing the reliance on glucose as a metabolic fuel, a hallmark of failing hearts. Furthermore, integrated omics signatures of ERRalpha loss-of-function and doxorubicin treatment exhibit common features of chemotherapeutic cardiotoxicity. These findings thus reveal potential cardiovascular risks in discrete combination therapies in the treatment of breast and other cancers. |
