Zhang Bingbing, Chen Yali, Gu Xuezhou, Zheng Yu, Jiang Zhong Hua
Department of Gastroenterology, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, The Yancheng Clinical Medical College of Jiangsu University, Yancheng, Jiangsu, 224006, China.
Department of General Surgery, Sheyang People's Hospital, Yancheng, Jiangsu, 224006, China.
BMC Cancer. 2025 May 22;25(1):923. doi: 10.1186/s12885-025-14340-4.
Ferroptosis is a novel iron-dependent type of programmed cell death that is characterized by the oxidation of lipids by divalent iron ions to produce lipid peroxides, which leads to cell death. Fucosyltransferase 11 (FUT11) is highly expressed in most tumors and is involved in tumorigenesis. However, there have been few studies regarding the relationship between FUT11 and ferroptosis. In this study, we found that FUT11 expression was abnormally high in gastric cancer (GC) cells and that the prognosis of patients with GC and high expression of FUT11 was poor. FUT11 expression was significantly correlated with the TNM stage of GC.Specific knockdown of FUT11 significantly inhibited the proliferation of GC cells, reduced the abundance of the key anti-ferroptotic protein glutathione peroxidase 4(GPX4), induced lipid peroxidation and ferroptosis in GC cells, and inhibited the proliferation of these cells. The overexpression of GPX4 reduced the inhibitory effect of FUT11 on GC cells. In addition, the knockdown of FUT11 significantly inhibited GC tumor growth in mice, and this inhibitory effect was reduced by the overexpression of GPX4. In conclusion, we have shown that FUT11 promotes GC progression by targeting GPX4, thereby inhibiting ferroptosis in GC cells. These findings suggest that FUT11 is a potential therapeutic target for GC.
铁死亡是一种新型的铁依赖性程序性细胞死亡，其特征是二价铁离子氧化脂质产生脂质过氧化物，从而导致细胞死亡。岩藻糖基转移酶11（FUT11）在大多数肿瘤中高表达，并参与肿瘤发生。然而，关于FUT11与铁死亡之间的关系，研究较少。在本研究中，我们发现FUT11在胃癌（GC）细胞中表达异常高，且FUT11高表达的GC患者预后较差。FUT11表达与GC的TNM分期显著相关。特异性敲低FUT11可显著抑制GC细胞增殖，降低关键抗铁死亡蛋白谷胱甘肽过氧化物酶4（GPX4）的丰度，诱导GC细胞脂质过氧化和铁死亡，并抑制这些细胞的增殖。GPX4的过表达降低了FUT11对GC细胞的抑制作用。此外，敲低FUT11可显著抑制小鼠GC肿瘤生长，而GPX4的过表达可降低这种抑制作用。总之，我们表明FUT11通过靶向GPX4促进GC进展，从而抑制GC细胞中的铁死亡。这些发现表明FUT11是GC的潜在治疗靶点。
