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

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.