Targeting the MTFR1–DRP1 pathway inhibits tumor growth and enhances chemosensitivity in breast cancer

Breast cancer (BC) is among the most prevalent malignancies affecting women worldwide. Mitochondrial fission regulator 1 (MTFR1), a protein implicated in the regulation of mitochondrial fission and cellular respiration, remains uncharacterized in human BC. This study investigated the biological functions and molecular mechanisms of MTFR1 in BC. Our analyses revealed significantly elevated MTFR1 expression in BC tissues, which correlated with poor patient outcomes. Functionally, MTFR1 enhances BC cell proliferation and drives increased mitochondrial fission. Crucially, MTFR1-mediated cell growth depends on DRP1 activity. Transcriptomic sequencing (RNA sequencing) revealed a positive association between MTFR1 and the AKT/mTOR signalling pathway. Furthermore, MTFR1 expression influenced chemosensitivity; patients with high MTFR1 levels had lower rates of pathological complete response and worse outcomes following neoadjuvant chemotherapy. Collectively, our findings identify MTFR1 as a promising predictive biomarker for chemotherapy efficacy and suggest that targeting the oncogenic MTFR1–DRP1 axis is a novel therapeutic strategy for BC.