PLK1 stabilizes β-catenin to drive colorectal carcinogenesis through NFKB2-mediated transcriptional activation of USP2a and site-specific phosphorylation.

ABSTRACT: Rationale: The Wnt/β-catenin signaling pathway is crucial in driving colorectal cancer (CRC), but therapeutic targeting is difficult due to on-target toxicity and adaptive resistance. Polo-like kinase 1 (PLK1), an essential regulator of mitosis, is known to stabilize β-catenin in various cancers. However, its specific mechanistic role in CRC, especially regarding the regulation of β-catenin ubiquitination, remains unclear. Methods: We integrated RNA-seq co-expression analysis with functional studies in CRC models, employing coimmunoprecipitation, ubiquitination assays, luciferase reporter systems, site-directed mutagenesis, and in vivo xenograft experiments. Results: We identified a dual-axis mechanism through which PLK1 posttranslationally and transcriptionally

SUBMITTER: Li Y 

PROVIDER: S-EPMC12846735 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature