上皮-间充质转化（EMT）产生具有类癌干细胞（CSCs）特性的细胞。靶向EMT程序以选择性消除CSCs是改善癌症治疗的有希望的途径。水芦黍霉素（Sal），一种K+ / H+ 离子载体，被发现对CSC样细胞具有高度选择性，但其作用机制和选择性仍然不清楚。在这里，我们展示了Sal，类似于莫兰星和尼格雷星，扰乱了高尔基体（GA）的功能。Sal改变了GA相关基因的表达，并导致GA形态发生显著变化，特别是在经历EMT的细胞中。此外，GA扰乱剂严重影响蛋白质的翻译后修饰，包括蛋白质处理、糖基化和分泌。我们发现，GA扰乱剂引起的改变特异性地影响EMT细胞的存活性。总的来说，我们的工作揭示了与EMT相关的新型易感性，暗示了GA在EMT中的重要作用，而靶向GA代表了一种针对CSCs的新型治疗方法.© 2023. 发表于生物学家公司。

Epithelial-to-mesenchymal transition (EMT) gives rise to cells with properties similar to cancer stem cells (CSCs). Targeting the EMT program to selectively eliminate CSCs is a promising way to improve cancer therapy. Salinomycin (Sal), a K+/H+ ionophore, was identified as highly selective towards CSC-like cells, but its mechanism of action and selectivity remains elusive. Here we show that Sal, similarly to monensin and nigericin, disturbs the function of the Golgi apparatus (GA). Sal alters the expression of GA-related genes and leads to marked changes in GA morphology, particularly in cells that underwent EMT. Moreover, GA disturbing agents severely affect post-translational modifications of proteins, including protein processing, glycosylation, and secretion. We discover that the alterations induced by GA disturbing agents specifically affect the viability of EMT cells. Collectively, our work reveals a novel vulnerability related to the EMT, suggesting an important role for the GA in the EMT, while targeting the GA represents a novel therapeutic approach against CSCs.© 2023. Published by The Company of Biologists Ltd.