Breast cancer stem cell metabolism: metabolic plasticity and microenvironmental regulation

Abstract

Breast cancer stem cells (BCSCs) are a tumorigenic cell population implicated in tumor initiation, therapeutic resistance, metastasis, and disease recurrence. Increasing evidence indicates that metabolic reprogramming is a fundamental feature of BCSC biology, enabling these cells to adapt to changing environmental conditions while maintaining stem-like properties. BCSCs exhibit remarkable metabolic plasticity and can dynamically utilize glycolysis, oxidative phosphorylation, lipid metabolism, and amino acid metabolism depending on cellular state and microenvironmental cues. Their metabolic programs are further shaped by the tumor microenvironment, where adipocytes, fibroblasts, endothelial cells, and immune cells influence metabolic adaptation through nutrient exchange and paracrine signaling. In turn, BCSCs actively remodel their surrounding niche to promote tumor initiation, immune evasion, and metastatic colonization. In this review, we discuss the major metabolic pathways that sustain BCSC function, examine emerging mechanisms linking metabolic plasticity to microenvironmental regulation, and highlight current therapeutic strategies targeting metabolic vulnerabilities. Understanding how interconnected metabolic networks and niche-derived signals govern BCSC behavior may facilitate the development of more effective therapies to reduce breast cancer progression and recurrence.