Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1784692222507089920 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9030767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT tanakachihiro ezrinregulatesthecellsurfacelocalizationofpdl1inhec151cells AT koboritakuro ezrinregulatesthecellsurfacelocalizationofpdl1inhec151cells AT okadarie ezrinregulatesthecellsurfacelocalizationofpdl1inhec151cells AT doukunirina ezrinregulatesthecellsurfacelocalizationofpdl1inhec151cells AT tameishimayuka ezrinregulatesthecellsurfacelocalizationofpdl1inhec151cells AT urashimayoko ezrinregulatesthecellsurfacelocalizationofpdl1inhec151cells AT itotakuya ezrinregulatesthecellsurfacelocalizationofpdl1inhec151cells AT takagakinobumasa ezrinregulatesthecellsurfacelocalizationofpdl1inhec151cells AT obatatokio ezrinregulatesthecellsurfacelocalizationofpdl1inhec151cells |