Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai, China.
Glycoconj J. 2024 Oct;41(4-5):229-240. doi: 10.1007/s10719-024-10167-6. Epub 2024 Oct 2.
Receiver for Activated C Kinase 1 (RACK1) is a highly conserved scaffold protein that can assemble multiple kinases and proteins together to form complexes, thereby regulating signal transduction process and various cellular biological processes, including cell cycle regulation, differentiation, and immune response. However, the function and mechanism of RACK1 in cervical cancer remain incompletely understood. Here we identified that RACK1 could significantly suppress cell ferroptosis in cervical cancer cells. Mechanistically, RACK1 increased the expression of FUT8 by inhibiting miR-1275, which in turn promoted the FUT8-catalyzed core-fucosylation of cystine/glutamate antiporter SLC7A11, thereby inhibiting SLC7A11 degradation and cell ferroptosis. Our data highlight the role of RACK1 in cervical cancer progression and its suppression of ferroptosis via the RACK1/miR-1275/FUT8/SLC7A11 axis, suggesting that inhibiting this pathway may be a promising therapeutic approach for patients with cervical cancer.
激活蛋白激酶 1（RACK1）受体是一种高度保守的支架蛋白，它可以将多种激酶和蛋白质组装在一起形成复合物，从而调节信号转导过程和各种细胞生物学过程，包括细胞周期调控、分化和免疫反应。然而，RACK1 在宫颈癌中的功能和机制仍不完全清楚。在这里，我们发现 RACK1 可以显著抑制宫颈癌细胞的铁死亡。在机制上，RACK1 通过抑制 miR-1275 增加了 FUT8 的表达，进而促进了胱氨酸/谷氨酸反向转运蛋白 SLC7A11 的核心岩藻糖基化，从而抑制了 SLC7A11 的降解和细胞铁死亡。我们的数据强调了 RACK1 在宫颈癌进展中的作用及其通过 RACK1/miR-1275/FUT8/SLC7A11 轴抑制铁死亡的作用，表明抑制这条通路可能是宫颈癌患者有前途的治疗方法。
