The polyamine transporter ATP13A3 mediates difluoromethylornithine-induced polyamine uptake in neuroblastoma.

ABSTRACT: High-risk neuroblastomas, often associated with MYCN protooncogene amplification, are addicted to polyamines, small polycations vital for cellular functioning. We have previously shown that neuroblastoma cells increase polyamine uptake when exposed to the polyamine biosynthesis inhibitor difluoromethylornithine (DFMO), and this mechanism is thought to limit the efficacy of the drug in clinical trials. This finding resulted in the clinical development of polyamine transport inhibitors, including AMXT 1501, which is presently under clinical investigation in combination with DFMO. However, the mechanisms and transporters involved in DFMO-induced polyamine uptake are unknown. Here, we report that knockdown of ATPase 13A3 (ATP13A3), a member of the P5B-ATPase polyamine transporter family, limit

SUBMITTER: Azfar M 

PROVIDER: S-EPMC11887671 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature