RSPO4 exerts tumor suppression through antagonizing canonical and non-canonical Wnt signaling.

ABSTRACT: R-spondins are a family of four secretory proteins reported to be Wnt agonists. Among them, R-spondin 4 (RSPO4) is unique, with the lowest binding affinity towards ZNRF3/RNF43 and the lowest efficacy in regulating Wnt/β-catenin signaling. RSPO4 has been shown to play important roles in nail development, liver fibrogenesis and periodontitis, while its role in cancerous context remains largely unknown. In this study, we performed multi-omic analysis on transcriptional expression and methylation pattern of RSPO4. In vitro cell-based assays were performed to evaluate the functionality of RSPO4. Through cancer epigenomics, we identified RSPO4 as a candidate tumor suppressor with tumor-specific epigenetic inactivation. We further found that RSPO4 is readily expressed in huma

SUBMITTER: Du Z 

PROVIDER: S-EPMC12781852 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature