PNPO-Mediated Oxidation of DVL3 Promotes Multiple Myeloma Malignancy and Osteoclastogenesis by Activating the Wnt/β-Catenin Pathway.

ABSTRACT: Multiple myeloma (MM) is a cancer of plasma cells caused by abnormal gene expression and interactions within the bone marrow (BM) niche. The BM environment significantly influences the progression of MM. Celastrol, a natural compound derived from traditional Chinese medicine, exhibits significant anticancer effects. This study aimed to identify specific targets of celastrol and develop more effective and less toxic treatment options for MM. Celastrol is used as a probe to determine its specific target, pyridoxine-5'-phosphate oxidase (PNPO). Increased levels of PNPO are associated with poor outcomes in MM patients, and PNPO promotes MM cell proliferation and induces osteoclast differentiation through exosomes. Mechanistically, PNPO oxidizes disheveled 3^M282 (DVL3), leading to ab

SUBMITTER: Deng Z 

PROVIDER: S-EPMC11792023 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature