Transcriptional induction of NF-κB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cells
Abstract The prognosis of high-grade gliomas, such as glioblastoma multiforme (GBM), is extremely poor due to the highly invasive nature of these aggressive cancers. Previous work has demonstrated that TNF-weak like factor (TWEAK) induction of the noncanonical NF-κB pathway promotes the invasiveness...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-38996-9 |
| _version_ | 1797576605046931456 |
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| author | Kathryn M. Pflug Dong W. Lee Kassandra McFadden Linda Herrera Raquel Sitcheran |
| author_facet | Kathryn M. Pflug Dong W. Lee Kassandra McFadden Linda Herrera Raquel Sitcheran |
| author_sort | Kathryn M. Pflug |
| collection | DOAJ |
| description | Abstract The prognosis of high-grade gliomas, such as glioblastoma multiforme (GBM), is extremely poor due to the highly invasive nature of these aggressive cancers. Previous work has demonstrated that TNF-weak like factor (TWEAK) induction of the noncanonical NF-κB pathway promotes the invasiveness of GBM cells in an NF-κB-inducing kinase (NIK)-dependent manner. While NIK activity is predominantly regulated at the posttranslational level, we show here that NIK (MAP3K14) is upregulated at the transcriptional level in invading cell populations, with the highest NIK expression observed in the most invasive cells. GBM cells with high induction of NIK gene expression demonstrate characteristics of collective invasion, facilitating invasion of neighboring cells. Furthermore, we demonstrate that the E2F transcription factors E2F4 and E2F5 directly regulate NIK transcription and are required to promote GBM cell invasion in response to TWEAK. Overall, our findings demonstrate that transcriptional induction of NIK facilitates collective cell migration and invasion, thereby promoting GBM pathogenesis. |
| first_indexed | 2024-03-10T21:55:20Z |
| format | Article |
| id | doaj.art-328459193936475a9bd7821b9e0a224e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T21:55:20Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-328459193936475a9bd7821b9e0a224e2023-11-19T13:08:45ZengNature PortfolioScientific Reports2045-23222023-08-0113111010.1038/s41598-023-38996-9Transcriptional induction of NF-κB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cellsKathryn M. Pflug0Dong W. Lee1Kassandra McFadden2Linda Herrera3Raquel Sitcheran4Department of Cell Biology and Genetics, School of Medicine, Texas A&M University Health Science CenterDepartment of Cell Biology and Genetics, School of Medicine, Texas A&M University Health Science CenterDepartment of Cell Biology and Genetics, School of Medicine, Texas A&M University Health Science CenterDepartment of Cell Biology and Genetics, School of Medicine, Texas A&M University Health Science CenterDepartment of Cell Biology and Genetics, School of Medicine, Texas A&M University Health Science CenterAbstract The prognosis of high-grade gliomas, such as glioblastoma multiforme (GBM), is extremely poor due to the highly invasive nature of these aggressive cancers. Previous work has demonstrated that TNF-weak like factor (TWEAK) induction of the noncanonical NF-κB pathway promotes the invasiveness of GBM cells in an NF-κB-inducing kinase (NIK)-dependent manner. While NIK activity is predominantly regulated at the posttranslational level, we show here that NIK (MAP3K14) is upregulated at the transcriptional level in invading cell populations, with the highest NIK expression observed in the most invasive cells. GBM cells with high induction of NIK gene expression demonstrate characteristics of collective invasion, facilitating invasion of neighboring cells. Furthermore, we demonstrate that the E2F transcription factors E2F4 and E2F5 directly regulate NIK transcription and are required to promote GBM cell invasion in response to TWEAK. Overall, our findings demonstrate that transcriptional induction of NIK facilitates collective cell migration and invasion, thereby promoting GBM pathogenesis.https://doi.org/10.1038/s41598-023-38996-9 |
| spellingShingle | Kathryn M. Pflug Dong W. Lee Kassandra McFadden Linda Herrera Raquel Sitcheran Transcriptional induction of NF-κB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cells Scientific Reports |
| title | Transcriptional induction of NF-κB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cells |
| title_full | Transcriptional induction of NF-κB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cells |
| title_fullStr | Transcriptional induction of NF-κB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cells |
| title_full_unstemmed | Transcriptional induction of NF-κB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cells |
| title_short | Transcriptional induction of NF-κB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cells |
| title_sort | transcriptional induction of nf κb inducing kinase by e2f4 5 facilitates collective invasion of gbm cells |
| url | https://doi.org/10.1038/s41598-023-38996-9 |
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