Erianin regulates programmed cell death ligand 1 expression and enhances cytotoxic T lymphocyte activity

Yang, Ankun; Li, Ming Yue; Zhang, Zhi Hong; Wang, Jing Ying; Xing, Yue; Ri, MyongHak; Jin, Cheng; Xu, Guang; Piao, Lian Xun; Jin, Hong; Zuo, Hong Xiang; Ma, Juan; Jin, Xuejun

doi:10.1016/j.jep.2020.113598

Cited by 30 publications

(23 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we observed the expressions of ezrin, radixin, moesin, and PD-L1 in HeLa cells at both mRNA and protein levels, all of which are in line with the previous observations using HeLa cells [ 44 , 45 , 48 , 49 ]. In another human cervical cancer cell line, OMC4, all three ERM were detected at protein levels, but the relative expression levels of radixin and moesin were lower than that of ezrin [ 50 ].…”

Section: Discussionsupporting

confidence: 92%

“…Interestingly, we demonstrated, for the first time, the colocalization of PD-L1 with all three ERM proteins in the plasma membrane of cancer cells. Recent studies have shown that PD-L1 is specifically distributed in the plasma membrane in HeLa cells [ 44 ], and that all the ERM proteins were colocalized with the actin cytoskeleton, indicating the plasma membrane localization of ERM in HeLa cells [ 45 , 46 , 47 , 51 , 52 ]. Taken together, PD-L1 and ERM are expressed at gene and protein levels and are colocalized in the plasma membrane of HeLa cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ezrin Modulates the Cell Surface Expression of Programmed Cell Death Ligand-1 in Human Cervical Adenocarcinoma Cells

et al. 2021

View full text Add to dashboard Cite

Cancer cells employ programmed cell death ligand-1 (PD-L1), an immune checkpoint protein that binds to programmed cell death-1 (PD-1) and is highly expressed in various cancers, including cervical carcinoma, to abolish T-cell-mediated immunosurveillance. Despite a key role of PD-L1 in various cancer cell types, the regulatory mechanism for PD-L1 expression is largely unknown. Understanding this mechanism could provide a novel strategy for cervical cancer therapy. Here, we investigated the influence of ezrin/radixin/moesin (ERM) family scaffold proteins, crosslinking the actin cytoskeleton and certain plasma membrane proteins, on the expression of PD-L1 in HeLa cells. Our results showed that all proteins were expressed at mRNA and protein levels and that all ERM proteins were highly colocalized with PD-L1 in the plasma membrane. Interestingly, immunoprecipitation assay results demonstrated that PD-L1 interacted with ERM as well as actin cytoskeleton proteins. Furthermore, gene silencing of ezrin, but not radixin and moesin, remarkably decreased the protein expression of PD-L1 without affecting its mRNA expression. In conclusion, ezrin may function as a scaffold protein for PD-L1; regulate PD-L1 protein expression, possibly via post-translational modification in HeLa cells; and serve as a potential therapeutic target for cervical cancer, improving the current immune checkpoint blockade therapy.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Ezrin Modulates the Cell Surface Expression of Programmed Cell Death Ligand-1 in Human Cervical Adenocarcinoma Cells

et al. 2021

View full text Add to dashboard Cite

show abstract

“…We also detected the gene and protein expression of PD-L1 in LS180 cells, which was similar with previous observations indicating the protein expression of PD-L1 in human CRC cell lines HCT116, LOVO, and HCT15 [ 53 , 54 ]. Furthermore, our CLSM analysis demonstrated, for the first time, the specific distribution of all three ERM proteins and PD-L1 in the plasma membrane of LS180 cells due to colocalization of PD-L1 with all three ERM proteins.…”

Section: Discussionsupporting

confidence: 91%

Role of Ezrin/Radixin/Moesin in the Surface Localization of Programmed Cell Death Ligand-1 in Human Colon Adenocarcinoma LS180 Cells

et al. 2021

View full text Add to dashboard Cite

Programmed cell death ligand-1 (PD-L1), an immune checkpoint protein highly expressed on the cell surface in various cancer cell types, binds to programmed cell death-1 (PD-1), leading to T-cell dysfunction and tumor survival. Despite clinical successes of PD-1/PD-L1 blockade therapies, patients with colorectal cancer (CRC) receive little benefit because most cases respond poorly. Because high PD-L1 expression is associated with immune evasion and poor prognosis in CRC patients, identifying potential modulators for the plasma membrane localization of PD-L1 may represent a novel therapeutic strategy for enhancing the efficacy of PD-1/PD-L1 blockade therapies. Here, we investigated whether PD-L1 expression in human colorectal adenocarcinoma cells (LS180) is affected by ezrin/radixin/moesin (ERM), functioning as scaffold proteins that crosslink plasma membrane proteins with the actin cytoskeleton. We observed colocalization of PD-L1 with all three ERM proteins in the plasma membrane and detected interactions involving PD-L1, the three ERM proteins, and the actin cytoskeleton. Furthermore, gene silencing of ezrin and radixin, but not of moesin, substantially decreased the expression of PD-L1 on the cell surface without affecting its mRNA level. Thus, in LS180 cells, ezrin and radixin may function as scaffold proteins mediating the plasma membrane localization of PD-L1, possibly by post-translational modification.

show abstract

“…Erianin induces oxidative stress, leading to apoptosis via the intrinsic apoptosis pathway (14)(15)(16)(17)(18), blocks the cell cycle at the G2/M phase (12,14,17), and has been recently found to trigger ferroptosis, an iron-dependent programmed cell death (19). In addition, treatment of nude mice with erianin significantly inhibit the growth of lung cancer, osteosarcoma, colorectal cancer and bladder cancer xenografts (14,16,17,(19)(20)(21). However, the anti-tumor effects of erianin in PCa have not been examined.…”

Section: Introductionmentioning

confidence: 99%

Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

et al. 2021

View full text Add to dashboard Cite

Prostate cancer is the second most prevalent malignancy worldwide. In the early stages, the development of prostate cancer is dependent on androgens. Over time with androgen deprivation therapy, 20% of prostate cancers progress to a castration-resistant form. Novel treatments for prostate cancers are still urgently needed. Erianin is a plant-derived bibenzyl compound. We report herein that erianin exhibits anti-tumor effects in androgen-sensitive and castration-resistant prostate cancer cells through different mechanisms. Erianin induces endoplasmic reticulum stress-associated apoptosis in androgen-sensitive prostate cancer cells. It also triggers pro-survival autophagic responses, as inhibition of autophagy predisposes to apoptosis. In contrast, erianin fails to induce apoptosis in castration-resistant prostate cancer cells. Instead, it results in cell cycle arrest at the M phase. Mechanistically, C16 ceramide dictates differential responses of androgen-sensitive and castration-resistant prostate cancer cells to erianin. Erianin elevates C16 ceramide level in androgen-sensitive but not castration-resistant prostate cancer cells. Overexpression of ceramide synthase 5 that specifically produces C16 ceramide enables erianin to induce apoptosis in castration-resistant prostate cancer cells. Our study provides both experimental evidence and mechanistic data showing that erianin is a potential treatment option for prostate cancers.

show abstract

Erianin regulates programmed cell death ligand 1 expression and enhances cytotoxic T lymphocyte activity

Cited by 30 publications

References 51 publications

Ezrin Modulates the Cell Surface Expression of Programmed Cell Death Ligand-1 in Human Cervical Adenocarcinoma Cells

Ezrin Modulates the Cell Surface Expression of Programmed Cell Death Ligand-1 in Human Cervical Adenocarcinoma Cells

Role of Ezrin/Radixin/Moesin in the Surface Localization of Programmed Cell Death Ligand-1 in Human Colon Adenocarcinoma LS180 Cells

Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

Contact Info

Product

Resources

About