Wang Jiefu, Gong Ziqing, Liu Jia, Wang Wenpeng, Liu Kai, Yang Yanpeng, Lu Xinran, Wang Junfeng
Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Peking University Health Science Center, Beijing, China.
BMC Cancer. 2025 Mar 19;25(1):507. doi: 10.1186/s12885-025-13873-y.
The Fc fragment of IgG binding protein (FCGBP) exhibits differential expression across various tumor types. but its role in cancer progression remains underexplored. This research discovered that FCGBP is downregulated in colorectal cancer (CRC) cells and is negatively associated with poor prognosis. Overexpression of FCGBP inhibited the growth of P53 wild-type CRC cells both in vitro and in vivo. Mechanistically, immunoprecipitation experiments revealed that FCGBP competitively binds to MDM2, thereby attenuating the formation of the P53/MDM2 complex. This, in turn, reduces P53 ubiquitination and stabilizes the protein. Our findings reveal a novel mechanism through which FCGBP significantly inhibits CRC cell growth and propose a new targeted therapeutic strategy for CRC treatment.
免疫球蛋白G结合蛋白（FCGBP）的Fc片段在多种肿瘤类型中表现出差异表达。但其在癌症进展中的作用仍未得到充分研究。本研究发现，FCGBP在结直肠癌（CRC）细胞中表达下调，且与预后不良呈负相关。FCGBP的过表达在体外和体内均抑制了P53野生型CRC细胞的生长。从机制上讲，免疫沉淀实验表明，FCGBP与MDM2竞争性结合，从而减弱P53/MDM2复合物的形成。这反过来又减少了P53的泛素化并稳定了该蛋白。我们的研究结果揭示了FCGBP显著抑制CRC细胞生长的新机制，并为CRC治疗提出了新的靶向治疗策略。
