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Updated: Jul 20, 2025
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
Salinomycin disturbs Golgi function and specifically affects cells in epithelial-to-mesenchymal transition
Marko Marjanović1, Ana-Matea Mikecin Dražić1, Marija Mioč1
1Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia.
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.
Insights
Salinomycin targets Golgi function to selectively eliminate cancer stem cell-like cells arising from epithelial-to-mesenchymal transition (EMT). This reveals a novel therapeutic strategy targeting the Golgi for improved cancer treatment.
Area of Science:
- Cell Biology
- Cancer Research
- Biochemistry
Background:
- Epithelial-to-mesenchymal transition (EMT) generates cancer stem cell-like properties.
- Targeting EMT is a promising strategy for cancer therapy.
- Salinomycin (Sal) selectively targets cancer stem cell-like cells, but its mechanism is unknown.
Purpose of the Study:
- Investigate the mechanism of Salinomycin's selective toxicity towards EMT-generated cancer stem cells.
- Determine the role of the Golgi apparatus in EMT and cancer stem cell biology.
- Explore targeting the Golgi as a novel therapeutic approach.
Main Methods:
- Treatment of EMT cells with Salinomycin and other Golgi-disturbing agents (monensin, nigericin).
- Analysis of Golgi morphology and gene expression.
- Assessment of protein post-translational modifications (processing, glycosylation, secretion).
- Evaluation of cell viability in response to Golgi disruption.
Main Results:
- Salinomycin and other Golgi-disrupting agents alter Golgi morphology and gene expression in EMT cells.
- These agents impair protein post-translational modifications, including processing, glycosylation, and secretion.
- Golgi disruption specifically reduces the viability of EMT-generated cells.
- This highlights a novel vulnerability associated with EMT.
Conclusions:
- The Golgi apparatus plays a critical role in EMT.
- Targeting Golgi function selectively eliminates cancer stem cell-like cells.
- Disrupting the Golgi represents a potential new therapeutic strategy against cancer stem cells.
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