Heart failure may promote breast cancer progression through a Col10a1-associated Tgf-β/Smad-EMT pathway

Abstract

Heart failure (HF) is clinically associated with aggravated breast cancer (BC) progression; however, the integrative genomic mechanisms underlying this cardio-oncological crosstalk remain poorly understood. We conducted integrative bioinformatics analyses combining weighted gene co-expression network analysis (WGCNA) and machine learning algorithms to screen key hub genes involved in HF and BC progression. The candidate gene Col10a1 was further validated using myocardial infarction (MI)-induced HF xenograft mouse models, paired clinical plasma and tumor specimens, and comprehensive in vitro functional assays. COL10A1 expression was higher in breast cancer patients with CVD than in BC-only patients. Given the limited sample size, these findings were considered exploratory. Mechanistically, elevated Col10a1 was associated with activation of the transforming growth factor‑β (Tgf-β)/Smad signaling pathway and induction of epithelial–mesenchymal transition (EMT). In vivo, the HF microenvironment markedly accelerated BC tumor growth and was accompanied by enhanced Col10a1 expression and Tgf-β signaling activation. In vitro, cardiomyocyte-derived Col10a1 significantly promoted the proliferation, migration, and invasion of BC cells, whereas Col10a1 knockdown significantly attenuated these malignant phenotypes. Our study identifies a potential regulatory link between HF and BC and provides preliminary mechanistic insights into the role of Col10a1 in BC progression under cardiac injury conditions. Col10a1 may serve as a candidate mediator in the interaction between cardiac injury and BC progression.