NPM1 phosphorylation-mediated telomere maintenance via stabilization of POLD3 in ALT-positive osteosarcoma: unraveling mechanisms and therapeutic opportunities.

ABSTRACT: Maintaining telomere integrity is essential for cellular survival, and reactivation of telomerase or alternative lengthening of telomeres (ALT) represents a hallmark of cancer, ensuring replicative immortality. Osteosarcoma (OS), a malignancy in which many tumors rely on ALT for telomere maintenance, lacks effective therapeutic strategies targeting this pathway. This study aimed to identify and characterize novel molecular regulators of ALT activity and explore their potential as therapeutic targets in OS. Methods: Immunohistochemistry was performed to evaluate the expression of phosphorylated NPM1 (pT199-NPM1) in OS tissues. Functional experiments including NPM1 knockdown and rescue assays were conducted to assess the impact of NPM1 on break-induced telomere replication (BITR) and

SUBMITTER: Zhao R 

PROVIDER: S-EPMC12905828 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature