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

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.