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...
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2019
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| _version_ | 1864513554078498816 |
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| author | Pramod Darvin (153341) |
| author2 | Varun Sasidharan Nair (5396393) Eyad Elkord (14150214) |
| author2_role | author author |
| author_facet | Pramod Darvin (153341) Varun Sasidharan Nair (5396393) Eyad Elkord (14150214) |
| author_role | author |
| dc.creator.none.fl_str_mv | Pramod Darvin (153341) Varun Sasidharan Nair (5396393) Eyad Elkord (14150214) |
| dc.date.none.fl_str_mv | 2019-02-19T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1155/2019/3958908 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/PD-L1_Expression_in_Human_Breast_Cancer_Stem_Cells_Is_Epigenetically_Regulated_through_Posttranslational_Histone_Modifications/22082729 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Medical biotechnology Oncology and carcinogenesis Tumor cancer therapy stem cells breast cancer cells histone acetylation enzymes |
| dc.title.none.fl_str_mv | PD-L1 Expression in Human Breast Cancer Stem Cells Is Epigenetically Regulated through Posttranslational Histone Modifications |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <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> |
| eu_rights_str_mv | openAccess |
| id | Manara2_1f8d05af6db7cc6cb55a03d6ff41e032 |
| identifier_str_mv | 10.1155/2019/3958908 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/22082729 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
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| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | PD-L1 Expression in Human Breast Cancer Stem Cells Is Epigenetically Regulated through Posttranslational Histone ModificationsPramod Darvin (153341)Varun Sasidharan Nair (5396393)Eyad Elkord (14150214)Biomedical and clinical sciencesMedical biotechnologyOncology and carcinogenesisTumorcancer therapystem cellsbreast cancer cellshistone acetylation enzymes<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>2019-02-19T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1155/2019/3958908https://figshare.com/articles/journal_contribution/PD-L1_Expression_in_Human_Breast_Cancer_Stem_Cells_Is_Epigenetically_Regulated_through_Posttranslational_Histone_Modifications/22082729CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/220827292019-02-19T06:00:00Z |
| spellingShingle | PD-L1 Expression in Human Breast Cancer Stem Cells Is Epigenetically Regulated through Posttranslational Histone Modifications Pramod Darvin (153341) Biomedical and clinical sciences Medical biotechnology Oncology and carcinogenesis Tumor cancer therapy stem cells breast cancer cells histone acetylation enzymes |
| status_str | publishedVersion |
| title | PD-L1 Expression in Human Breast Cancer Stem Cells Is Epigenetically Regulated through Posttranslational Histone Modifications |
| title_full | PD-L1 Expression in Human Breast Cancer Stem Cells Is Epigenetically Regulated through Posttranslational Histone Modifications |
| title_fullStr | PD-L1 Expression in Human Breast Cancer Stem Cells Is Epigenetically Regulated through Posttranslational Histone Modifications |
| title_full_unstemmed | PD-L1 Expression in Human Breast Cancer Stem Cells Is Epigenetically Regulated through Posttranslational Histone Modifications |
| title_short | PD-L1 Expression in Human Breast Cancer Stem Cells Is Epigenetically Regulated through Posttranslational Histone Modifications |
| title_sort | PD-L1 Expression in Human Breast Cancer Stem Cells Is Epigenetically Regulated through Posttranslational Histone Modifications |
| topic | Biomedical and clinical sciences Medical biotechnology Oncology and carcinogenesis Tumor cancer therapy stem cells breast cancer cells histone acetylation enzymes |