Ubiquitin E3 ligase KPC1 governs mesenchymal metastatic melanoma reprogramming via proteasomal degradation of ZEB1.

ABSTRACT: Metastatic melanoma (MM) displays remarkable phenotypic plasticity, allowing tumor cells to transition reversibly between proliferative and mesenchymal (MES)-like states. This dynamic switching is strongly associated with therapeutic resistance and poor prognosis. Although transcriptional and epigenetic mechanisms driving these transitions have been extensively studied, the role of post-translational regulation, particularly the ubiquitin-proteasome system, remains poorly understood. Here, we identify the ubiquitin E3 ligase RNF 123 (KPC1) as a key post-translational suppressor of MES reprogramming in MM. Integrative analyses of bulk and single-cell transcriptomic datasets revealed that KPC1 expression is inversely correlated with the expression of core mesenchymal markers such as ZEB1, CD

SUBMITTER: Nakano Y 

PROVIDER: S-EPMC12722757 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature