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Ezrin Regulates the Cell Surface Localization of PD-L1 in HEC-151 Cells

Programmed death ligand-1 (PD-L1) is an immune checkpoint molecule widely expressed on the surface of cancer cells and is an attractive immunotherapeutic target for numerous cancer cell types. However, patients with endometrial cancer derive little clinical benefit from immune checkpoint blockade th...

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Autores principales: Tanaka, Chihiro, Kobori, Takuro, Okada, Rie, Doukuni, Rina, Tameishi, Mayuka, Urashima, Yoko, Ito, Takuya, Takagaki, Nobumasa, Obata, Tokio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030767/
https://www.ncbi.nlm.nih.gov/pubmed/35456317
http://dx.doi.org/10.3390/jcm11082226
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author Tanaka, Chihiro
Kobori, Takuro
Okada, Rie
Doukuni, Rina
Tameishi, Mayuka
Urashima, Yoko
Ito, Takuya
Takagaki, Nobumasa
Obata, Tokio
author_facet Tanaka, Chihiro
Kobori, Takuro
Okada, Rie
Doukuni, Rina
Tameishi, Mayuka
Urashima, Yoko
Ito, Takuya
Takagaki, Nobumasa
Obata, Tokio
author_sort Tanaka, Chihiro
collection PubMed
description Programmed death ligand-1 (PD-L1) is an immune checkpoint molecule widely expressed on the surface of cancer cells and is an attractive immunotherapeutic target for numerous cancer cell types. However, patients with endometrial cancer derive little clinical benefit from immune checkpoint blockade therapy because of their poor response rate. Despite the increasingly important function of PD-L1 in tumor immunology, the mechanism of PD-L1 localization on endometrial cancer cell surfaces is largely unknown. We demonstrated the contribution of the ezrin, radixin, and moesin (ERM) family, which consists of scaffold proteins that control the cell surface localization of several transmembrane proteins to the localization of PD-L1 on the cell surface of HEC-151, a human uterine endometrial cancer cell line. Confocal immunofluorescence microscopy and immunoprecipitation analysis revealed the colocalization of all the ERM with PD-L1 on the cell surface, as well as their protein–protein interactions. The RNA-interference-mediated knockdown of ezrin, but not radixin and moesin, significantly reduced the cell surface expression of PD-L1, as measured by flow cytometry, with little impact on the PD-L1 mRNA expression. In conclusion, among the three ERM proteins present in HEC-151 cells, ezrin may execute the scaffold function for PD-L1 and may be mainly responsible for the cell surface localization of PD-L1, presumably via the post-translational modification process.
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spelling pubmed-90307672022-04-23 Ezrin Regulates the Cell Surface Localization of PD-L1 in HEC-151 Cells Tanaka, Chihiro Kobori, Takuro Okada, Rie Doukuni, Rina Tameishi, Mayuka Urashima, Yoko Ito, Takuya Takagaki, Nobumasa Obata, Tokio J Clin Med Article Programmed death ligand-1 (PD-L1) is an immune checkpoint molecule widely expressed on the surface of cancer cells and is an attractive immunotherapeutic target for numerous cancer cell types. However, patients with endometrial cancer derive little clinical benefit from immune checkpoint blockade therapy because of their poor response rate. Despite the increasingly important function of PD-L1 in tumor immunology, the mechanism of PD-L1 localization on endometrial cancer cell surfaces is largely unknown. We demonstrated the contribution of the ezrin, radixin, and moesin (ERM) family, which consists of scaffold proteins that control the cell surface localization of several transmembrane proteins to the localization of PD-L1 on the cell surface of HEC-151, a human uterine endometrial cancer cell line. Confocal immunofluorescence microscopy and immunoprecipitation analysis revealed the colocalization of all the ERM with PD-L1 on the cell surface, as well as their protein–protein interactions. The RNA-interference-mediated knockdown of ezrin, but not radixin and moesin, significantly reduced the cell surface expression of PD-L1, as measured by flow cytometry, with little impact on the PD-L1 mRNA expression. In conclusion, among the three ERM proteins present in HEC-151 cells, ezrin may execute the scaffold function for PD-L1 and may be mainly responsible for the cell surface localization of PD-L1, presumably via the post-translational modification process. MDPI 2022-04-15 /pmc/articles/PMC9030767/ /pubmed/35456317 http://dx.doi.org/10.3390/jcm11082226 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tanaka, Chihiro
Kobori, Takuro
Okada, Rie
Doukuni, Rina
Tameishi, Mayuka
Urashima, Yoko
Ito, Takuya
Takagaki, Nobumasa
Obata, Tokio
Ezrin Regulates the Cell Surface Localization of PD-L1 in HEC-151 Cells
title Ezrin Regulates the Cell Surface Localization of PD-L1 in HEC-151 Cells
title_full Ezrin Regulates the Cell Surface Localization of PD-L1 in HEC-151 Cells
title_fullStr Ezrin Regulates the Cell Surface Localization of PD-L1 in HEC-151 Cells
title_full_unstemmed Ezrin Regulates the Cell Surface Localization of PD-L1 in HEC-151 Cells
title_short Ezrin Regulates the Cell Surface Localization of PD-L1 in HEC-151 Cells
title_sort ezrin regulates the cell surface localization of pd-l1 in hec-151 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030767/
https://www.ncbi.nlm.nih.gov/pubmed/35456317
http://dx.doi.org/10.3390/jcm11082226
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