PD-L1 Expression in Human Breast Cancer Stem Cells Is Epigenetically Regulated through Posttranslational Histone Modifications
<p>Tumor progression through immune evasion is a major challenge in cancer therapy. Recent studies revealed that enhanced PD-L1 expression in cancer stem cells is linked to immune evasion. Understanding the mechanisms behind this PD-L1 overexpression in cancer stem cells is critical for develo...
محفوظ في:
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| مؤلفون آخرون: | , |
| منشور في: |
2019
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| الموضوعات: | |
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إضافة وسم
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| الملخص: | <p>Tumor progression through immune evasion is a major challenge in cancer therapy. Recent studies revealed that enhanced PD-L1 expression in cancer stem cells is linked to immune evasion. Understanding the mechanisms behind this PD-L1 overexpression in cancer stem cells is critical for developing more effective strategies for preventing immune evasion and increasing the efficacy of anti-PD-1/PD-L1 therapy. Tumorsphere formation in breast cancer cells enhanced epithelial to mesenchymal transition (EMT), which is evident by increased expression of mesenchymal markers. In this study, we analyzed CpG methylation of PD-L1 promoter in MCF-7 and BT-549 breast cancer cells and tumorspheres derived from them. PD-L1 promoter was significantly hypomethylated in MCF-7 tumorspheres, but not from BT-549 tumorspheres, compared with their cell line counterparts. The active demethylation of PD-L1 promoter was confirmed by the increase in the distribution of 5hmC and decrease in 5mC levels and the upregulation of TET3 and downregulation of DNMTs enzymes in MCF-7 tumorspheres, compared with the cell line. Additionally, we checked the distribution of repressive histones H3K9me3, H3K27me3, and active histone H3K4me3 in the PD-L1 promoter. We found that distribution of repressive histones to the PD-L1 promoter was lower in tumorspheres, compared with cell lines. Moreover, an overexpression of histone acetylation enzymes was observed in tumorspheres suggesting the active involvement of histone modifications in EMT-induced PD-L1 expression. In summary, EMT-associated overexpression of PD-L1 was partially independent of promoter CpG methylation and more likely to be dependent on posttranslational histone modifications. </p> <h2>Other information</h2> <p>Published in: Journal of Oncology<br> License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br> See article on publisher's website: <a href="http://dx.doi.org/10.1155/2019/3958908" target="_blank">http://dx.doi.org/10.1155/2019/3958908</a></p> |
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