Ezrin Regulates the Cell Surface Localization of PD-L1 in HEC-151 Cells
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- Chihiro Tanaka
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Japan
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- Takuro Kobori
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Japan
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- Rie Okada
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Japan
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- Rina Doukuni
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Japan
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- Mayuka Tameishi
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Japan
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- Yoko Urashima
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Japan
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- Takuya Ito
- Laboratory of Natural Medicines, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Japan
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- Nobumasa Takagaki
- Nobumasa Clinic, Kyoto 601-8041, Japan
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- Tokio Obata
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Japan
説明
<jats:p>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.</jats:p>
収録刊行物
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- Journal of Clinical Medicine
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Journal of Clinical Medicine 11 (8), 2226-, 2022-04-15
MDPI AG