Salinomycin disturbs Golgi function and specifically affects cells in epithelial-to-mesenchymal transition

Marjanović, Marko; Mikecin Dražić, Ana-Matea; Mioč, Marija; Paradžik, Mladen; Kliček, Filip; Novokmet, Mislav; Lauc, Gordan; Kralj, Marijeta (2023) Salinomycin disturbs Golgi function and specifically affects cells in epithelial-to-mesenchymal transition. Journal of Cell Science, 136 (17). ISSN 1477-9137

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Abstract

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, similar to monensin and nigericin, disturbs the function of the Golgi. Sal alters the expression of Golgi-related genes and leads to marked changes in Golgi morphology, particularly in cells that have undergone EMT. Moreover, Golgi-disturbing agents severely affect post-translational modifications of proteins, including protein processing, glycosylation and secretion. We discover that the alterations induced by Golgi-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 Golgi in the EMT and that targeting the Golgi could represent a novel therapeutic approach against CSCs.

Item Type:

Article

Uncontrolled Keywords:

EMT; Breast CSCs; Golgi; ER; Salinomycin; Monensin; N-glycosylation

Subjects:

NATURAL SCIENCES > Biology
NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences

Divisions:

Division of Molecular Medicine

Projects: