FBXO22-mediated ubiquitination of KLF10 promoting pancreatic cancer proliferation and invasion

BACKGROUND: Pancreatic cancer (PC) is a highly aggressive cancer with poor clinical outcomes. F-box only protein 22 (FBXO22), as an integral part of the SCF E3 ubiquitin ligase complex, has been associated with various cancers, but its role in PC remains underexplored. METHODS: FBXO22 expression in pancreatic cancer tissues and adjacent normal tissues was analyzed by bioinformatics and validated using quantitative real-time PCR (qPCR). Functional assays, including proliferation, invasion, and apoptosis analyses, were conducted in pancreatic cancer cell lines following FBXO22 overexpression or knockdown. Mass spectrometry-based proteomic profiling was performed to identify potential ubiquitination targets of FBXO22. The interaction between FBXO22 and candidate targets was confirmed by co-immunoprecipitation, western blotting, and ubiquitination assays. The in vivo role of FBXO22 in pancreatic tumor progression was further evaluated using a xenograft model in BALB/c nude mice. RESULTS: FBXO22 was significantly overexpressed in pancreatic cancer tissues compared to adjacent normal tissues. FBXO22 overexpression enhanced pancreatic cancer cell proliferation and invasion, whereas its knockdown suppressed these oncogenic properties. Mass spectrometry identified KLF10 as a potential substrate of FBXO22-mediated ubiquitination. Further experiments confirmed that FBXO22 promotes KLF10 degradation via the ubiquitin-proteasome pathway. Overexpression of KLF10 suppressed pancreatic cancer cell proliferation and induced apoptosis through the TGF-β signaling pathway. In vivo, FBXO22 knockdown significantly inhibited pancreatic tumor growth and increased KLF10 expression. CONCLUSION: FBXO22 promotes pancreatic cancer progression by mediating KLF10 ubiquitination and degradation, thereby impairing its tumor-suppressive functions. FBXO22 may serve as a potential oncogenic and therapeutic target associated with pancreatic cancer progression.