Disrupting Lipid Raft Microdomains to Block Polyploid Giant Cancer Cell Budding and Enhance Radiotherapy Response.

ABSTRACT: Radiotherapy failure often arises from tumor repopulation by treatment-resistant cancer cells. Following irradiation, cancer cells can undergo endoreplication to form polyploid giant cancer cells (PGCCs)-radiation-persistent cells capable of generating progeny through a virus-like asymmetric budding process. While such membrane budding is evolutionarily conserved across archaea, viruses, and eukaryotic cells, its molecular mechanism in cancer remains poorly defined. Here, a radiation-induced SNCG-FLOT2-CHMP4B signaling axis is identified as a key regulator of PGCC budding. Mechanistically, ASAH1 and SMPD2 maintain sphingolipid metabolic balance, while FLOT2 drives germination at lipid raft-enriched membrane microdomains, followed by CHMP4B-dependent abscission to release daughter cells. Di

SUBMITTER: Deng Z 

PROVIDER: S-EPMC12904004 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature