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Salinomycin affects Golgi apparatus function in cancer stem-like cells

Cancer stem cells (CSC) are an immortal tumor-initiating population that can selfrenew and has pluripotent capacity. Despite their small number, CSCs are believed to be critical for tumor initiation, progression and metastasis, as well as for the treatment failure and disease relapse. CSCs have been confirmed to exist in various types of tumors which include leukemia as well as solid cancers. There are several obstacles involved with CSC research among which are their low number within tumor cell population and their relative instability in culture. Recently, a breast CSC model was established by experimental induction of epithelial to mesenchymal transition (EMT) in immortalized human mammary epithelial cells (HMLE). Using this model, salinomycin was identified to be selectively toxic towards epithelial CSCs. Salinomycin is a K+/H+ exchanger that can affect cation transport across different membranes present in the cell. However, the exact mechanism of the observed selectivity remains largely unknown. We have noticed that salinomycin affects postranslational modifications of membrane proteins in the aforementioned CSC model. This led us to the hypothesis that salinomycin induces Golgi apparatus stress that affects secretory pathway which may represent a key vulnerability of EMT cells. Of note, monensin, another ionophore with chemical structure similar to that of salinomycin, is a well described inhibitor of Golgi function.

cancer stem cells, salinomycin, Golgi apparatus, epithelial to mesenchymal transition

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