RIPK2 promotes colorectal cancer metastasis by protecting YAP degradation from ITCH-mediated ubiquitination.

ABSTRACT: Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide, making the exploration of metastatic mechanisms crucial for therapeutic advancements. In this study, we identified receptor-interacting protein kinase 2 (RIPK2) as an independent risk factor for poor CRC prognosis. Single-cell RNA sequencing and spatial transcriptomics revealed that a tumor cell cluster with high RIPK2 expression exhibited enhanced metastatic potential, closely linked to bacterial invasion. In vitro and in vivo experiments confirmed that RIPK2 specifically promotes tumor cell migration and invasion, rather than proliferation. Proteomic analysis indicated that RIPK2 knockdown leads to increased proteolysis mediated by ubiquitin, particularly affecting the oncoprotein YAP. Additionally, ba

SUBMITTER: Lu C 

PROVIDER: S-EPMC11971272 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature