Pathophysiological Roles of Actin-Binding Scaffold Protein, Ezrin

Kawaguchi, Kotoku; Asano, Shinji

doi:10.3390/ijms23063246

Cited by 33 publications

(28 citation statements)

References 101 publications

(112 reference statements)

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“…As post-translational factors, ERM proteins contribute to the cell surface localization of several cancer-related transmembrane proteins, such as epidermal growth factor receptor 2 and several drug transporters, by cross-linking them with the actin cytoskeleton [27,29,62,63]. Interestingly, our recent studies demonstrated that among the ERM proteins, ezrin predominantly controls the plasma membrane localization of PD-L1, possibly via molecular interaction, in human adenocarcinoma cells derived from uterine cervix (HeLa) and colorectum (LS180) cells, in which ezrin is expressed at the highest level among ERM, based on DepMap global gene expression analysis and RT-PCR data [31,32].…”

Section: Discussionmentioning

confidence: 99%

Moesin Serves as Scaffold Protein for PD-L1 in Human Uterine Cervical Squamous Carcinoma Cells

Doukuni

Kobori

Tanaka

et al. 2022

JCM

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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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Section: Discussionmentioning

confidence: 99%

Moesin Serves as Scaffold Protein for PD-L1 in Human Uterine Cervical Squamous Carcinoma Cells

Doukuni

Kobori

Tanaka

et al. 2022

JCM

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Section: 2mentioning

confidence: 99%

“…Ezrin is one of the members of the ezrin/radixin/moesin (ERM) family of proteins [86]. ERM proteins exert numerous physiological functions in morphogenesis, cell polarity, and modulation of cell membrane tension [86]. All these varied roles are carried out by ERM proteins by regulating the assembly of protein complexes at the cell surface.…”

Section: 2mentioning

confidence: 99%

“…All these varied roles are carried out by ERM proteins by regulating the assembly of protein complexes at the cell surface. Additionally, ezrin, which is localized at the cytoplasmic surface of cellular membranes, links plasma membrane proteins to the cortical actin cytoskeleton [86]. The role of ezrin in the pathogenesis of asthma is, as yet, poorly understood.…”

Section: 2mentioning

confidence: 99%

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Differences in Inflammatory Cytokine Profile in Obesity-Associated Asthma: Effects of Weight Loss

Bantulà

Tubita

Roca‐Ferrer

et al. 2022

JCM

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Obesity and asthma are associated with systemic inflammation maintained by mediators released by adipose tissue and lung. This study investigated the inflammatory serum mediator profile in obese subjects (O) (n = 35), non-obese asthma (NOA) patients (n = 14), obese asthmatics (OA) (n = 21) and healthy controls (HC) (n = 33). The effect of weight loss after bariatric surgery (BS) was examined in 10 OA and 31 O subjects. We analyzed serum markers including leptin, adiponectin, TGF-β1, TNFR2, MCP-1, ezrin, YKL-40, ST2, IL-5, IL-9, and IL-18. Compared with HC subjects, the O group showed increased levels of leptin, TGF-β1, TNFR2, MCP-1, ezrin, YKL-40, and ST2; the OA group presented increased levels of MCP-1, ezrin, YKL-40, and IL-18, and the NOA group had increased levels of ezrin, YKL-40, IL-5, and IL-18. The higher adiponectin/leptin ratio in NOA with respect to OA subjects was the only significant difference between the two groups. IL-9 was the only cytokine with significantly higher levels in OA with respect to O subjects. TNFR2, ezrin, MCP-1, and IL-18 concentrations significantly decreased in O subjects after BS. O, OA, and NOA showed distinct patterns of systemic inflammation. Leptin and adiponectin are regulated in asthma by obesity-dependent and -independent mechanisms. Combination of asthma and obesity does not result in significant additive effects on circulating cytokine levels.

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“…Tanaka C. and colleagues opened the issue and investigated the role of ezrin/radixin/moesin (ERM) family proteins, which have a high degree of sequence similarity with each other that crosslinks several cancer-related transmembrane proteins [ 23 , 24 , 25 , 26 ] with the actin cytoskeleton in the plasma membrane localization of PD-L1, utilizing HEC-151 cells derived from the human endometrial adenocarcinoma [ 27 ]. Tanaka C. et al discovered that all three ERM proteins were highly co-localized with PD-L1 in the surface plasma membrane of HEC-151 cells assessed via immunofluorescent staining with confocal laser scanning microscopy (CLSM), and that they interacted with PD-L1, as demonstrated by the immunoprecipitation assay using anti-PD-L1 antibody [ 27 ].…”

mentioning

confidence: 99%