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Molecules 2018, 23(2), 337; https://doi.org/10.3390/molecules23020337

Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors

1
Institute of Molecular Physiology and Genetics, Centre of Bioscience, Slovak Academy of Sciences, Dúbravska cesta 9, 84505 Bratislava, Slovakia
2
Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Dúbravska cesta 9, 84505 Bratislava, Slovakia
3
Institute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, 81237 Bratislava, Slovakia
*
Authors to whom correspondence should be addressed.
Received: 13 January 2018 / Revised: 30 January 2018 / Accepted: 1 February 2018 / Published: 6 February 2018
(This article belongs to the Special Issue Counteracting Drug Resistant Mechanisms in Cancer)
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Abstract

Multidrug resistance (MDR) is a phenotype of cancer cells with reduced sensitivity to a wide range of unrelated drugs. P-glycoprotein (P-gp)—a drug efflux pump (ABCB1 member of the ABC transporter gene family)—is frequently observed to be a molecular cause of MDR. The drug-efflux activity of P-gp is considered as the underlying mechanism of drug resistance against P-gp substrates and results in failure of cancer chemotherapy. Several pathological impulses such as shortages of oxygen and glucose supply, alterations of calcium storage mechanisms and/or processes of protein N-glycosylation in the endoplasmic reticulum (ER) leads to ER stress (ERS), characterized by elevation of unfolded protein cell content and activation of the unfolded protein response (UPR). UPR is responsible for modification of protein folding pathways, removal of misfolded proteins by ER associated protein degradation (ERAD) and inhibition of proteosynthesis. However, sustained ERS may result in UPR-mediated cell death. Neoplastic cells could escape from the death pathway induced by ERS by switching UPR into pro survival mechanisms instead of apoptosis. Here, we aimed to present state of the art information about consequences of P-gp expression on mechanisms associated with ERS development and regulation of the ERAD system, particularly focused on advances in ERS-associated therapy of drug resistant malignancies. View Full-Text
Keywords: multidrug resistance; P-glycoprotein; ER stress; unfolded protein response; ERAD; N-glycosylation; malignancies multidrug resistance; P-glycoprotein; ER stress; unfolded protein response; ERAD; N-glycosylation; malignancies
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Hano, M.; Tomášová, L.; Šereš, M.; Pavlíková, L.; Breier, A.; Sulová, Z. Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors. Molecules 2018, 23, 337.

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