SLC6A14 Drives Mitochondrial Fusion and Oxidative Phosphorylation to Promote Cancer Stemness and Early-Onset of Breast Cancer.

ABSTRACT: Early-onset breast cancer (EOBC), diagnosed before the age of 45, is associated with poor therapeutic outcomes and limited survival, yet the underlying mechanisms remain poorly defined. Identifying environmental risk factors and actionable therapeutic targets is an urgent clinical need. Notably, the largest survival gap between younger and older patients occurs in luminal breast cancer, implicating potential endocrine disruption. Here, an association is identified between elevated levels of di(2-ethylhexyl)phthalate (DEHP) in hair, a widely used endocrine-disrupting plasticizer, and earlier age at diagnosis of breast cancer. Mechanistically, DEHP exposure promotes tumor initiation by enhancing cancer stemness through mitochondrial fusion and glutamine-driven oxidative phosphorylation. DEHP

SUBMITTER: Hu DW 

PROVIDER: S-EPMC12677700 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature