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

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...

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Autores principales: Hano, Milan, Tomášová, Lenka, Šereš, Mário, Pavlíková, Lucia, Breier, Albert, Sulová, Zdena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017601/
https://www.ncbi.nlm.nih.gov/pubmed/29415493
http://dx.doi.org/10.3390/molecules23020337
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author Hano, Milan
Tomášová, Lenka
Šereš, Mário
Pavlíková, Lucia
Breier, Albert
Sulová, Zdena
author_facet Hano, Milan
Tomášová, Lenka
Šereš, Mário
Pavlíková, Lucia
Breier, Albert
Sulová, Zdena
author_sort Hano, Milan
collection PubMed
description 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.
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spelling pubmed-60176012018-11-13 Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors Hano, Milan Tomášová, Lenka Šereš, Mário Pavlíková, Lucia Breier, Albert Sulová, Zdena Molecules Review 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. MDPI 2018-02-06 /pmc/articles/PMC6017601/ /pubmed/29415493 http://dx.doi.org/10.3390/molecules23020337 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hano, Milan
Tomášová, Lenka
Šereš, Mário
Pavlíková, Lucia
Breier, Albert
Sulová, Zdena
Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors
title Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors
title_full Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors
title_fullStr Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors
title_full_unstemmed Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors
title_short Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors
title_sort interplay between p-glycoprotein expression and resistance to endoplasmic reticulum stressors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017601/
https://www.ncbi.nlm.nih.gov/pubmed/29415493
http://dx.doi.org/10.3390/molecules23020337
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