PRODH2-Mediated Metabolism in the Bone Microenvironment Promotes Breast Cancer Metastasis.

ABSTRACT: Breast cancer frequently metastasizes to the bone, but treatment options for bone metastatic breast cancer are limited. Amino acid metabolism is reprogrammed in the bone metastatic microenvironment, suggesting that it could represent a therapeutic vulnerability. In this study, we focused on the metabolism of hydroxyproline (Hyp), a key amino acid resulting from bone collagen degradation, which serves as a critical biomarker for bone metastases. Proline dehydrogenase 2 (PRODH2), the primary enzyme involved in Hyp metabolism, was significantly upregulated in clinical samples from breast cancer bone metastases. Notably, PRODH2-mediated Hyp metabolism drove osteoclast differentiation, enhancing collagen degradation and promoting breast cancer bone metastasis in vivo. Furthermore, PRODH2 facili

SUBMITTER: Gong H 

PROVIDER: S-EPMC12580816 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature