PKA-Mediated Phosphorylation of SFRP4 Promotes Wnt/β-Catenin Activation and Cancer Stemness in Gastric Cancer.

ABSTRACT: Secreted Frizzled-related protein 4 (SFRP4) has been identified as a patient-level biomarker of the stem-like subtype of gastric cancer (GC), which is associated with poor prognosis and resistance to chemotherapy. Although multiple studies have documented the clinical significance of SFRP4 in GC, its mechanistic role in the stem-like subtype remains incompletely understood. In this study, we elucidate how phosphorylation of SFRP4 by protein kinase A (PKA) converts it into a Wnt signaling agonist. We began with a phosphoproteomic database search to identify candidate kinases that phosphorylate SFRP4. Co-immunoprecipitation assays revealed a direct interaction between PKA and SFRP4, and in vitro kinase assays confirmed that PKA phosphorylates SFRP4 at key threonine residues. Phosphorylated S

SUBMITTER: Jhe YL 

PROVIDER: S-EPMC12192866 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature