STAMBP drives colorectal cancer progression via CXCR4 deubiquitination and bone marrow-derived suppressor cell recruitment

Abstract

Colorectal cancer (CRC) is one of the three leading causes of tumor-related mortality worldwide. The recruitment of bone marrow-derived suppressor cells (MDSCs) is a key mechanism by which tumors evade immune surveillance, as these cells inhibit T cell activity and accelerate CRC progression. STAMBP, a member of the Jab1/MPN metalloenzyme family of deubiquitinases (DUBs), cleaves K63-linked polyubiquitin chains from protein substrates and participates in diverse physiological and pathological processes. Nevertheless, its role in CRC and the mechanisms through which it contributes to disease progression have not been clearly defined. In the present study, we observed that both STAMBP and MDSCs were significantly upregulated in CRC tissues and cell lines. Functional assays revealed that STAMBP promotes CRC cell proliferation while simultaneously enhancing MDSC recruitment. Mechanistic analysis demonstrated that STAMBP regulates the deubiquitination of CXCR4, which stabilizes its protein expression. Silencing of CXCR4 not only suppressed CRC cell growth but also diminished MDSC infiltration. In conclusion, these findings indicate that STAMBP facilitates CRC progression through CXCR4 stabilization and MDSCs recruitment, highlighting a potential target for therapeutic intervention.