NF-κB/p52 augments ETS1 binding genome-wide to promote glioma progression
Gliomas are highly invasive and chemoresistant cancers, making them challenging to treat. Chronic inflammation is a key driver of glioma progression as it promotes aberrant activation of inflammatory pathways such as NF-κB signalling, which drives cancer cell invasion and angiogenesis. NF-κB factors...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Online Access: | https://hdl.handle.net/10356/169293 |
| _version_ | 1811689721605128192 |
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| author | Sim, Nicholas Li, Yinghui |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Sim, Nicholas Li, Yinghui |
| author_sort | Sim, Nicholas |
| collection | NTU |
| description | Gliomas are highly invasive and chemoresistant cancers, making them challenging to treat. Chronic inflammation is a key driver of glioma progression as it promotes aberrant activation of inflammatory pathways such as NF-κB signalling, which drives cancer cell invasion and angiogenesis. NF-κB factors typically dimerise with its own family members, but emerging evidence of their promiscuous interactions with other oncogenic factors has been reported to promote transcription of new target genes and function. Here, we show that non-canonical NF-κB activation directly regulates p52 at the ETS1 promoter, activating its expression. This impacts the genomic and transcriptional landscape of ETS1 in a glioma-specific manner. We further show that enhanced non-canonical NF-κB signalling promotes the co-localisation of p52 and ETS1, resulting in transcriptional activation of non-κB and/or non-ETS glioma-promoting genes. We conclude that p52-induced ETS1 overexpression in glioma cells remodels the genome-wide regulatory network of p52 and ETS1 to transcriptionally drive cancer progression. |
| first_indexed | 2024-10-01T05:52:36Z |
| format | Journal Article |
| id | ntu-10356/169293 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:52:36Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1692932023-07-17T15:31:52Z NF-κB/p52 augments ETS1 binding genome-wide to promote glioma progression Sim, Nicholas Li, Yinghui School of Biological Sciences Institute of Molecular and Cell Biology (IMCB), A*STAR Science::Biological sciences Glioma ETS1 Protein Gliomas are highly invasive and chemoresistant cancers, making them challenging to treat. Chronic inflammation is a key driver of glioma progression as it promotes aberrant activation of inflammatory pathways such as NF-κB signalling, which drives cancer cell invasion and angiogenesis. NF-κB factors typically dimerise with its own family members, but emerging evidence of their promiscuous interactions with other oncogenic factors has been reported to promote transcription of new target genes and function. Here, we show that non-canonical NF-κB activation directly regulates p52 at the ETS1 promoter, activating its expression. This impacts the genomic and transcriptional landscape of ETS1 in a glioma-specific manner. We further show that enhanced non-canonical NF-κB signalling promotes the co-localisation of p52 and ETS1, resulting in transcriptional activation of non-κB and/or non-ETS glioma-promoting genes. We conclude that p52-induced ETS1 overexpression in glioma cells remodels the genome-wide regulatory network of p52 and ETS1 to transcriptionally drive cancer progression. Nanyang Technological University National Research Foundation (NRF) Published version This work is supported by the National Research Foundation (NRF), Singapore, under the Singapore NRF Fellowship (NRF-NRFF2018-04). Additionally, we thank Nanyang Technological University for the PhD scholarship support of N.S. and Nanyang Assistant Professorship start-up grant to Y.L. lab. 2023-07-11T06:29:49Z 2023-07-11T06:29:49Z 2023 Journal Article Sim, N. & Li, Y. (2023). NF-κB/p52 augments ETS1 binding genome-wide to promote glioma progression. Communications Biology, 6(1), 445-. https://dx.doi.org/10.1038/s42003-023-04821-2 2399-3642 https://hdl.handle.net/10356/169293 10.1038/s42003-023-04821-2 37087499 2-s2.0-85153550455 1 6 445 en NRF-NRFF2018-04 Nanyang Assistant Professorship (NAP) Communications Biology © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. application/pdf |
| spellingShingle | Science::Biological sciences Glioma ETS1 Protein Sim, Nicholas Li, Yinghui NF-κB/p52 augments ETS1 binding genome-wide to promote glioma progression |
| title | NF-κB/p52 augments ETS1 binding genome-wide to promote glioma progression |
| title_full | NF-κB/p52 augments ETS1 binding genome-wide to promote glioma progression |
| title_fullStr | NF-κB/p52 augments ETS1 binding genome-wide to promote glioma progression |
| title_full_unstemmed | NF-κB/p52 augments ETS1 binding genome-wide to promote glioma progression |
| title_short | NF-κB/p52 augments ETS1 binding genome-wide to promote glioma progression |
| title_sort | nf κb p52 augments ets1 binding genome wide to promote glioma progression |
| topic | Science::Biological sciences Glioma ETS1 Protein |
| url | https://hdl.handle.net/10356/169293 |
| work_keys_str_mv | AT simnicholas nfkbp52augmentsets1bindinggenomewidetopromotegliomaprogression AT liyinghui nfkbp52augmentsets1bindinggenomewidetopromotegliomaprogression |