PDK1-dependent metabolic reprogramming regulates stemness and tumorigenicity of osteosarcoma stem cells through ATF3.

ABSTRACT: Osteosarcoma stem cells (OSCs) are characterized by their self-renewal and multilineage differentiation abilities, contributing to osteosarcoma malignancy. The Warburg effect describes cancer cells' preference for glycolysis over mitochondrial oxidative phosphorylation (OXPHOS) for energy production. Unlike differentiated cancer cells, cancer stem cells exhibit unique and diverse metabolic properties depending on the context. This study investigated the metabolic reliance of OSCs and related genes through in silico analyses of clinical osteosarcoma specimens and in vitro and in vivo genetic and pharmacological analyses. Glycolysis and OXPHOS pathways were more active in OSCs than in non-OSCs at single-cell resolution. Pyruvate dehydrogenase kinase 1 (PDK1), a key enzyme balancing glycolysi

SUBMITTER: Tokumura K 

PROVIDER: S-EPMC12307947 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature