Correlations of mRNA Levels among Efflux Transporters, Transcriptional Regulators, and Scaffold Proteins in Non-Small-Cell Lung Cancer

Multidrug resistance (MDR) due to enhanced drug efflux activity of tumor cells can severely impact the efficacy of antitumor therapies. We recently showed that increased activity of the efflux transporter P-glycoprotein (P-gp) associated with activation of Snail transcriptional regulators may be med...

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Main Authors: Xieyi Zhang, Wangyang Liu, Kazue Edaki, Yuta Nakazawa, Hiroki Kamioka, Atsushi Fujita, Ryoichi Onozato, Misa Iijima, Shigeru Tsuchida, Takahiro Arai, Yukiyoshi Fujita, Kenta Mizoi, Takuo Ogihara
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Canadian Journal of Infectious Diseases and Medical Microbiology
Online Access:http://dx.doi.org/10.1155/2021/4005327
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author Xieyi Zhang
Wangyang Liu
Kazue Edaki
Yuta Nakazawa
Hiroki Kamioka
Atsushi Fujita
Ryoichi Onozato
Misa Iijima
Shigeru Tsuchida
Takahiro Arai
Yukiyoshi Fujita
Kenta Mizoi
Takuo Ogihara
author_facet Xieyi Zhang
Wangyang Liu
Kazue Edaki
Yuta Nakazawa
Hiroki Kamioka
Atsushi Fujita
Ryoichi Onozato
Misa Iijima
Shigeru Tsuchida
Takahiro Arai
Yukiyoshi Fujita
Kenta Mizoi
Takuo Ogihara
author_sort Xieyi Zhang
collection DOAJ
description Multidrug resistance (MDR) due to enhanced drug efflux activity of tumor cells can severely impact the efficacy of antitumor therapies. We recently showed that increased activity of the efflux transporter P-glycoprotein (P-gp) associated with activation of Snail transcriptional regulators may be mediated mainly by moesin in lung cancer cells. Here, we aimed to systematically evaluate the relationships among mRNA expression levels of efflux transporters (P-gp, breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2)), scaffold proteins (ezrin (Ezr), radixin (Rdx), and moesin (Msn); ERM proteins), and SNAI family members (Snail, Slug, and Smac) in clinical lung cancer and noncancer samples. We found high correlations between relative (cancer/noncancer) mRNA expression levels of Snail and Msn, Msn and P-gp, Slug and MRP2, and Smuc and BCRP. These findings support our previous conclusion that Snail regulates P-gp activity via Msn and further suggest that Slug and Smuc may contribute to the functional regulation of MRP2 and BCRP, respectively, in lung cancer cells. This trial is registered with UMIN000023923.
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spelling doaj-art-69d15ea92e944128a255dbaa3e7dfa6b2025-08-20T03:34:05ZengWileyCanadian Journal of Infectious Diseases and Medical Microbiology1918-14932021-01-01202110.1155/2021/4005327Correlations of mRNA Levels among Efflux Transporters, Transcriptional Regulators, and Scaffold Proteins in Non-Small-Cell Lung CancerXieyi Zhang0Wangyang Liu1Kazue Edaki2Yuta Nakazawa3Hiroki Kamioka4Atsushi Fujita5Ryoichi Onozato6Misa Iijima7Shigeru Tsuchida8Takahiro Arai9Yukiyoshi Fujita10Kenta Mizoi11Takuo Ogihara12Laboratory of BiopharmaceuticsLaboratory of Clinical PharmacokineticsLaboratory of BiopharmaceuticsLaboratory of BiopharmaceuticsLaboratory of Clinical PharmacokineticsDepartment of General Thoracic SurgeryDepartment of General Thoracic SurgeryDepartment of Pathology and Clinical LaboratoriesDivision of Clinical LaboratoryDivision of PharmacyDivision of PharmacyLaboratory of BiopharmaceuticsLaboratory of BiopharmaceuticsMultidrug resistance (MDR) due to enhanced drug efflux activity of tumor cells can severely impact the efficacy of antitumor therapies. We recently showed that increased activity of the efflux transporter P-glycoprotein (P-gp) associated with activation of Snail transcriptional regulators may be mediated mainly by moesin in lung cancer cells. Here, we aimed to systematically evaluate the relationships among mRNA expression levels of efflux transporters (P-gp, breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2)), scaffold proteins (ezrin (Ezr), radixin (Rdx), and moesin (Msn); ERM proteins), and SNAI family members (Snail, Slug, and Smac) in clinical lung cancer and noncancer samples. We found high correlations between relative (cancer/noncancer) mRNA expression levels of Snail and Msn, Msn and P-gp, Slug and MRP2, and Smuc and BCRP. These findings support our previous conclusion that Snail regulates P-gp activity via Msn and further suggest that Slug and Smuc may contribute to the functional regulation of MRP2 and BCRP, respectively, in lung cancer cells. This trial is registered with UMIN000023923.http://dx.doi.org/10.1155/2021/4005327
spellingShingle Xieyi Zhang
Wangyang Liu
Kazue Edaki
Yuta Nakazawa
Hiroki Kamioka
Atsushi Fujita
Ryoichi Onozato
Misa Iijima
Shigeru Tsuchida
Takahiro Arai
Yukiyoshi Fujita
Kenta Mizoi
Takuo Ogihara
Correlations of mRNA Levels among Efflux Transporters, Transcriptional Regulators, and Scaffold Proteins in Non-Small-Cell Lung Cancer
Canadian Journal of Infectious Diseases and Medical Microbiology
title Correlations of mRNA Levels among Efflux Transporters, Transcriptional Regulators, and Scaffold Proteins in Non-Small-Cell Lung Cancer
title_full Correlations of mRNA Levels among Efflux Transporters, Transcriptional Regulators, and Scaffold Proteins in Non-Small-Cell Lung Cancer
title_fullStr Correlations of mRNA Levels among Efflux Transporters, Transcriptional Regulators, and Scaffold Proteins in Non-Small-Cell Lung Cancer
title_full_unstemmed Correlations of mRNA Levels among Efflux Transporters, Transcriptional Regulators, and Scaffold Proteins in Non-Small-Cell Lung Cancer
title_short Correlations of mRNA Levels among Efflux Transporters, Transcriptional Regulators, and Scaffold Proteins in Non-Small-Cell Lung Cancer
title_sort correlations of mrna levels among efflux transporters transcriptional regulators and scaffold proteins in non small cell lung cancer
url http://dx.doi.org/10.1155/2021/4005327
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