Increased Expression of the Δ133p53β Isoform Enhances Brain Metastasis
The Δ133p53β isoform is increased in many primary tumors and has many tumor-promoting properties that contribute to increased proliferation, migration and inflammation. Here we investigated whether Δ133p53β contributed to some of the most aggressive tumors that had metastasized to the brain. <i&g...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1267 |
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| author | Alexandra N. Boix De Jesus Ahmad Taha David Wang Paulomi M. Mehta Sunali Mehta Ashley Reily-Bell Sasini Polwatta Lekamlage Adriana Machado Saraiva Tahmeed Tahmeedzaman Fouzia Ziad Ziad Thotathil Peter Y. C. Gan Janice Royds Antony Braithwaite Noelyn Hung Tania L. Slatter |
| author_facet | Alexandra N. Boix De Jesus Ahmad Taha David Wang Paulomi M. Mehta Sunali Mehta Ashley Reily-Bell Sasini Polwatta Lekamlage Adriana Machado Saraiva Tahmeed Tahmeedzaman Fouzia Ziad Ziad Thotathil Peter Y. C. Gan Janice Royds Antony Braithwaite Noelyn Hung Tania L. Slatter |
| author_sort | Alexandra N. Boix De Jesus |
| collection | DOAJ |
| description | The Δ133p53β isoform is increased in many primary tumors and has many tumor-promoting properties that contribute to increased proliferation, migration and inflammation. Here we investigated whether Δ133p53β contributed to some of the most aggressive tumors that had metastasized to the brain. <i>Δ133p53β</i> mRNA expression was measured in lung, breast, melanoma, colorectal metastases and, where available, the matched primary tumor. The presence of <i>Δ133p53β</i> expression was associated with the time for the primary tumor to metastasize and overall survival once the tumor was detected in the brain. <i>Δ133p53β</i> was present in over 50% of lung, breast, melanoma and colorectal metastases to the brain. It was also increased in the brain metastases compared with the matched primary tumor. Brain metastases with <i>Δ133p53β</i> expressed were associated with a reduced time for the primary tumor to metastasize to the brain compared with tumors with no <i>Δ133p53β</i> expression. In-vitro-based analyses in Δ133p53β-expressing cells showed increased cancer-promoting proteins on the cell surface and increased downstream p-AKT and p-MAPK signaling. Δ133p53β-expressing cells also invaded more readily across a mock blood–brain barrier. Together these data suggested that Δ133p53β contributes to brain metastases by making cells more likely to invade the brain. |
| first_indexed | 2024-03-09T12:24:08Z |
| format | Article |
| id | doaj.art-cd15a027d6564bfbb11b42e61f1f5fa0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:24:08Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cd15a027d6564bfbb11b42e61f1f5fa02023-11-30T22:37:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242126710.3390/ijms24021267Increased Expression of the Δ133p53β Isoform Enhances Brain MetastasisAlexandra N. Boix De Jesus0Ahmad Taha1David Wang2Paulomi M. Mehta3Sunali Mehta4Ashley Reily-Bell5Sasini Polwatta Lekamlage6Adriana Machado Saraiva7Tahmeed Tahmeedzaman8Fouzia Ziad9Ziad Thotathil10Peter Y. C. Gan11Janice Royds12Antony Braithwaite13Noelyn Hung14Tania L. Slatter15Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandDepartment of Neurosurgery, Southern District Health Board, Dunedin 9016, New ZealandDepartment of Medicine, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandDepartment of Pathology, Waikato District Health Board, Hamilton 3204, New ZealandDepartment of Radiation Oncology, Waikato District Health Board, Hamilton 3204, New ZealandDepartment of Neurosurgery, Waikato District Health Board, Hamilton 3204, New ZealandDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New ZealandThe Δ133p53β isoform is increased in many primary tumors and has many tumor-promoting properties that contribute to increased proliferation, migration and inflammation. Here we investigated whether Δ133p53β contributed to some of the most aggressive tumors that had metastasized to the brain. <i>Δ133p53β</i> mRNA expression was measured in lung, breast, melanoma, colorectal metastases and, where available, the matched primary tumor. The presence of <i>Δ133p53β</i> expression was associated with the time for the primary tumor to metastasize and overall survival once the tumor was detected in the brain. <i>Δ133p53β</i> was present in over 50% of lung, breast, melanoma and colorectal metastases to the brain. It was also increased in the brain metastases compared with the matched primary tumor. Brain metastases with <i>Δ133p53β</i> expressed were associated with a reduced time for the primary tumor to metastasize to the brain compared with tumors with no <i>Δ133p53β</i> expression. In-vitro-based analyses in Δ133p53β-expressing cells showed increased cancer-promoting proteins on the cell surface and increased downstream p-AKT and p-MAPK signaling. Δ133p53β-expressing cells also invaded more readily across a mock blood–brain barrier. Together these data suggested that Δ133p53β contributes to brain metastases by making cells more likely to invade the brain.https://www.mdpi.com/1422-0067/24/2/1267p53 isoformΔ133p53βbrainmetastasistime to metastasisreceptor recycling |
| spellingShingle | Alexandra N. Boix De Jesus Ahmad Taha David Wang Paulomi M. Mehta Sunali Mehta Ashley Reily-Bell Sasini Polwatta Lekamlage Adriana Machado Saraiva Tahmeed Tahmeedzaman Fouzia Ziad Ziad Thotathil Peter Y. C. Gan Janice Royds Antony Braithwaite Noelyn Hung Tania L. Slatter Increased Expression of the Δ133p53β Isoform Enhances Brain Metastasis International Journal of Molecular Sciences p53 isoform Δ133p53β brain metastasis time to metastasis receptor recycling |
| title | Increased Expression of the Δ133p53β Isoform Enhances Brain Metastasis |
| title_full | Increased Expression of the Δ133p53β Isoform Enhances Brain Metastasis |
| title_fullStr | Increased Expression of the Δ133p53β Isoform Enhances Brain Metastasis |
| title_full_unstemmed | Increased Expression of the Δ133p53β Isoform Enhances Brain Metastasis |
| title_short | Increased Expression of the Δ133p53β Isoform Enhances Brain Metastasis |
| title_sort | increased expression of the δ133p53β isoform enhances brain metastasis |
| topic | p53 isoform Δ133p53β brain metastasis time to metastasis receptor recycling |
| url | https://www.mdpi.com/1422-0067/24/2/1267 |
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