Salinomycin disturbs Golgi apparatus function and specifically affects cells in epithelial-to- mesenchymal transition (CROSBI ID 792317)
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Podaci o odgovornosti
Marjanović, Marko ; Dražić, Ana-Matea Mikecin ; Mioč, Marija ; Kliček, Filip ; Novokmet, Mislav ; Lauc, Gordan ; Kralj, Marijeta
engleski
Salinomycin disturbs Golgi apparatus function and specifically affects cells in epithelial-to- mesenchymal transition
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 protein post-translational modifications 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 identifies a new vulnerability related to the EMT, suggesting that targeting the GA is a novel therapeutic approach against CSCs.
EMT, breast CSCs, Golgi apparatus, ER, salinomycin, monensin, N-glycosylation
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Podaci o izdanju
BioRxiv
2022.
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objavljeno
2692-8205
Povezanost rada
Biologija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje), Farmacija, Kemija, Temeljne medicinske znanosti