Physiological Roles of ERM Proteins and Transcriptional Regulators in Supporting Membrane Expression of Efflux Transporters as Factors of Drug Resistance in Cancer
One factor contributing to the malignancy of cancer cells is the acquisition of drug resistance during chemotherapy via increased expression of efflux transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP). These tran...
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doaj-92c7dde4b02444c5bbfc6b43d15132b32020-11-25T04:06:01ZengMDPI AGCancers2072-66942020-11-01123352335210.3390/cancers12113352Physiological Roles of ERM Proteins and Transcriptional Regulators in Supporting Membrane Expression of Efflux Transporters as Factors of Drug Resistance in CancerTakuo Ogihara0Kenta Mizoi1Hiroki Kamioka2Kentaro Yano3Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare, 60, Nakaorui-machi, Takasaki, Gunma 370-0033, JapanFaculty of Pharmacy, Takasaki University of Health and Welfare, 60, Nakaorui-machi, Takasaki, Gunma 370-0033, JapanGraduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare, 60, Nakaorui-machi, Takasaki, Gunma 370-0033, JapanFaculty of Pharmacy, Takasaki University of Health and Welfare, 60, Nakaorui-machi, Takasaki, Gunma 370-0033, JapanOne factor contributing to the malignancy of cancer cells is the acquisition of drug resistance during chemotherapy via increased expression of efflux transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP). These transporters operate at the cell membrane, and are anchored in place by the scaffold proteins ezrin (Ezr), radixin (Rdx), and moesin (Msn) (ERM proteins), which regulate their functional activity. The identity of the regulatory scaffold protein(s) differs depending upon the transporter, and also upon the tissue in which it is expressed, even for the same transporter. Another factor contributing to malignancy is metastatic ability. Epithelial–mesenchymal transition (EMT) is the first step in the conversion of primary epithelial cells into mesenchymal cells that can be transported to other organs via the blood. The SNAI family of transcriptional regulators triggers EMT, and SNAI expression is used is an indicator of malignancy. Furthermore, EMT has been suggested to be involved in drug resistance, since drug excretion from cancer cells is promoted during EMT. We showed recently that ERM proteins are induced by a member of the SNAI family, Snail. Here, we first review recent progress in research on the relationship between efflux transporters and scaffold proteins, including the question of tissue specificity. In the second part, we review the relationship between ERM scaffold proteins and the transcriptional regulatory factors that induce their expression.https://www.mdpi.com/2072-6694/12/11/3352efflux transportersERM proteinstranscriptional regulatorsSNAI familyepithelial–mesenchymal transitionmembrane expression |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Takuo Ogihara Kenta Mizoi Hiroki Kamioka Kentaro Yano |
spellingShingle |
Takuo Ogihara Kenta Mizoi Hiroki Kamioka Kentaro Yano Physiological Roles of ERM Proteins and Transcriptional Regulators in Supporting Membrane Expression of Efflux Transporters as Factors of Drug Resistance in Cancer Cancers efflux transporters ERM proteins transcriptional regulators SNAI family epithelial–mesenchymal transition membrane expression |
author_facet |
Takuo Ogihara Kenta Mizoi Hiroki Kamioka Kentaro Yano |
author_sort |
Takuo Ogihara |
title |
Physiological Roles of ERM Proteins and Transcriptional Regulators in Supporting Membrane Expression of Efflux Transporters as Factors of Drug Resistance in Cancer |
title_short |
Physiological Roles of ERM Proteins and Transcriptional Regulators in Supporting Membrane Expression of Efflux Transporters as Factors of Drug Resistance in Cancer |
title_full |
Physiological Roles of ERM Proteins and Transcriptional Regulators in Supporting Membrane Expression of Efflux Transporters as Factors of Drug Resistance in Cancer |
title_fullStr |
Physiological Roles of ERM Proteins and Transcriptional Regulators in Supporting Membrane Expression of Efflux Transporters as Factors of Drug Resistance in Cancer |
title_full_unstemmed |
Physiological Roles of ERM Proteins and Transcriptional Regulators in Supporting Membrane Expression of Efflux Transporters as Factors of Drug Resistance in Cancer |
title_sort |
physiological roles of erm proteins and transcriptional regulators in supporting membrane expression of efflux transporters as factors of drug resistance in cancer |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-11-01 |
description |
One factor contributing to the malignancy of cancer cells is the acquisition of drug resistance during chemotherapy via increased expression of efflux transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP). These transporters operate at the cell membrane, and are anchored in place by the scaffold proteins ezrin (Ezr), radixin (Rdx), and moesin (Msn) (ERM proteins), which regulate their functional activity. The identity of the regulatory scaffold protein(s) differs depending upon the transporter, and also upon the tissue in which it is expressed, even for the same transporter. Another factor contributing to malignancy is metastatic ability. Epithelial–mesenchymal transition (EMT) is the first step in the conversion of primary epithelial cells into mesenchymal cells that can be transported to other organs via the blood. The SNAI family of transcriptional regulators triggers EMT, and SNAI expression is used is an indicator of malignancy. Furthermore, EMT has been suggested to be involved in drug resistance, since drug excretion from cancer cells is promoted during EMT. We showed recently that ERM proteins are induced by a member of the SNAI family, Snail. Here, we first review recent progress in research on the relationship between efflux transporters and scaffold proteins, including the question of tissue specificity. In the second part, we review the relationship between ERM scaffold proteins and the transcriptional regulatory factors that induce their expression. |
topic |
efflux transporters ERM proteins transcriptional regulators SNAI family epithelial–mesenchymal transition membrane expression |
url |
https://www.mdpi.com/2072-6694/12/11/3352 |
work_keys_str_mv |
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