快速增殖的癌细胞中的脂质代谢发生改变，其中脂肪酸 (FA) 用于合成鞘脂和甘油磷脂，以产生细胞膜和信号分子。活化 C 激酶 1 的受体（RACK1；也称为小核糖体亚基蛋白）是一种参与信号传导途径的细胞内支架蛋白。这种脂质代谢是否受 RACK1 调节尚不清楚。在这里，整合的空间解析代谢组学和空间转录组学揭示了宫颈癌（CC）样本中脂质的积累与 RACK1 的过度表达相关，并且 RACK1 促进了 CC 细胞中的脂质合成。染色质免疫沉淀验证了甾醇调节元件结合蛋白 1 (SREBP1) 与乙酰辅酶 A 羧化酶 (ACC) 和脂肪酸合酶 (FASN) 启动子的结合。 RACK1 通过上调甾醇调节元件结合转录因子 1 (SREBP1) 以及脂肪生成基因 FASN 和 ACC1 的表达来增强 FA 从头合成。免疫共沉淀和蛋白质印迹显示，RACK1 与蛋白激酶 B (AKT) 相互作用，激活 AKT/哺乳动物雷帕霉素靶蛋白 (mTOR)/SREBP1 信号通路，促进 FA 合成。细胞增殖和凋亡实验表明，RACK1 调节的 FA 合成是 CC 进展的关键。因此，RACK1通过AKT/mTOR/SREBP1信号通路增强脂质合成，促进CC细胞的生长。 RACK1 可能成为 CC 的治疗靶点。© 2024 作者。约翰·威利出版的《分子肿瘤学》

Lipid metabolism is altered in rapidly proliferating cancer cells, where fatty acids (FAs) are utilized in the synthesis of sphingolipids and glycerophospholipids to produce cell membranes and signaling molecules. Receptor for activated C-kinase 1 (RACK1; also known as small ribosomal subunit protein) is an intracellular scaffolding protein involved in signaling pathways. Whether such lipid metabolism is regulated by RACK1 is unknown. Here, integrated spatially resolved metabolomics and spatial transcriptomics revealed that accumulation of lipids in cervical cancer (CC) samples correlated with overexpression of RACK1, and RACK1 promoted lipid synthesis in CC cells. Chromatin immunoprecipitation verified binding of sterol regulatory element-binding protein 1 (SREBP1) to acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN) promoters. RACK1 enhanced de novo FA synthesis by upregulating expression of sterol regulatory element binding transcription factor 1 (SREBP1) and lipogenic genes FASN and ACC1. Co-immunoprecipitation and western blotting revealed that RACK1 interacted with protein kinase B (AKT) to activate the AKT/mammalian target of rapamycin (mTOR)/SREBP1 signaling pathway to promote FA synthesis. Cell proliferation and apoptosis experiments suggested that RACK1-regulated FA synthesis is key in the progression of CC. Thus, RACK1 enhanced lipid synthesis through the AKT/mTOR/SREBP1 signaling pathway to promote the growth of CC cells. RACK1 may become a therapeutic target for CC.© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.