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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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/8/2226 |
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| author | Chihiro Tanaka Takuro Kobori Rie Okada Rina Doukuni Mayuka Tameishi Yoko Urashima Takuya Ito Nobumasa Takagaki Tokio Obata |
| author_facet | Chihiro Tanaka Takuro Kobori Rie Okada Rina Doukuni Mayuka Tameishi Yoko Urashima Takuya Ito Nobumasa Takagaki Tokio Obata |
| author_sort | Chihiro Tanaka |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T04:33:10Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T04:33:10Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-a1d372570d464b1789385e64f252b9532023-12-03T13:33:04ZengMDPI AGJournal of Clinical Medicine2077-03832022-04-01118222610.3390/jcm11082226Ezrin Regulates the Cell Surface Localization of PD-L1 in HEC-151 CellsChihiro Tanaka0Takuro Kobori1Rie Okada2Rina Doukuni3Mayuka Tameishi4Yoko Urashima5Takuya Ito6Nobumasa Takagaki7Tokio Obata8Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, JapanLaboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, JapanLaboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, JapanLaboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, JapanLaboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, JapanLaboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, JapanLaboratory of Natural Medicines, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, JapanNobumasa Clinic, Kyoto 601-8041, JapanLaboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, JapanProgrammed 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.https://www.mdpi.com/2077-0383/11/8/2226programmed death ligand-1ezrinradixinmoesinendometrioid adenocarcinomaimmune checkpoint inhibitor |
| spellingShingle | Chihiro Tanaka Takuro Kobori Rie Okada Rina Doukuni Mayuka Tameishi Yoko Urashima Takuya Ito Nobumasa Takagaki Tokio Obata Ezrin Regulates the Cell Surface Localization of PD-L1 in HEC-151 Cells Journal of Clinical Medicine programmed death ligand-1 ezrin radixin moesin endometrioid adenocarcinoma immune checkpoint inhibitor |
| 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 | programmed death ligand-1 ezrin radixin moesin endometrioid adenocarcinoma immune checkpoint inhibitor |
| url | https://www.mdpi.com/2077-0383/11/8/2226 |
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