期刊
JOURNAL OF CLINICAL MEDICINE
卷 11, 期 13, 页码 -出版社
MDPI
DOI: 10.3390/jcm11133830
关键词
programmed death ligand-1; ezrin; radixin; moesin; uterine cervical squamous cancer; immune checkpoint inhibitor; cancer immunotherapy
资金
- Osaka Cancer Society
- Osaka Ohtani University Research Foundation
- JSPS KAKENHI [JP20K07118]
- Kobayashi Foundation
Moesin may be a scaffold protein responsible for the plasma membrane expression of PD-L1 in human uterine cervical SCC.
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.
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