Moesin Serves as Scaffold Protein for PD-L1 in Human Uterine Cervical Squamous Carcinoma Cells
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- Rina Doukuni
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Osaka, Japan
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- Takuro Kobori
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Osaka, Japan
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- Chihiro Tanaka
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Osaka, Japan
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- Mayuka Tameishi
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Osaka, Japan
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- Yoko Urashima
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Osaka, Japan
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- Takuya Ito
- Laboratory of Natural Medicines, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Osaka, Japan
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- Tokio Obata
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, Osaka, Japan
抄録
<jats:p>Immune checkpoint blockade (ICB) therapy targeting the programmed death ligand-1 (PD-L1)/PD-1 axis has emerged as a promising treatment for uterine cervical cancer; however, only a small subset of patients with uterine cervical squamous cell carcinoma (SCC) derives clinical benefit from ICB therapies. Thus, there is an urgent unmet medical need for novel therapeutic strategies to block the PD-L1/PD-1 axis in patients with uterine cervical SCC. Here, we investigated the involvement of ezrin/radixin/moesin (ERM) family scaffold proteins, which crosslink several plasma membrane proteins with the actin cytoskeleton, on the plasma membrane localization of PD-L1 in BOKU and HCS-2 cells derived from human uterine cervical SCC. Immunofluorescence analysis showed that PD-L1 colocalized with all three ERM proteins in the plasma membrane. Gene knockdown of moesin, but not ezrin and radixin, substantially reduced the plasma membrane expression of PD-L1, with limited effect on mRNA expression. An immunoprecipitation assay demonstrated the molecular interaction between PD-L1 and moesin. Moreover, phosphorylated, i.e., activated, moesin was highly colocalized with PD-L1 in the plasma membrane. In conclusion, moesin may be a scaffold protein responsible for the plasma membrane expression of PD-L1 in human uterine cervical SCC.</jats:p>
収録刊行物
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- Journal of Clinical Medicine
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Journal of Clinical Medicine 11 (13), 3830-, 2022-07-01
MDPI AG