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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. Δ133p53...

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Autores principales: Jesus, Alexandra N. Boix De, Taha, Ahmad, Wang, David, Mehta, Paulomi M., Mehta, Sunali, Reily-Bell, Ashley, Lekamlage, Sasini Polwatta, Saraiva, Adriana Machado, Tahmeedzaman, Tahmeed, Ziad, Fouzia, Thotathil, Ziad, Gan, Peter Y. C., Royds, Janice, Braithwaite, Antony, Hung, Noelyn, Slatter, Tania L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866425/
https://www.ncbi.nlm.nih.gov/pubmed/36674782
http://dx.doi.org/10.3390/ijms24021267
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author Jesus, Alexandra N. Boix De
Taha, Ahmad
Wang, David
Mehta, Paulomi M.
Mehta, Sunali
Reily-Bell, Ashley
Lekamlage, Sasini Polwatta
Saraiva, Adriana Machado
Tahmeedzaman, Tahmeed
Ziad, Fouzia
Thotathil, Ziad
Gan, Peter Y. C.
Royds, Janice
Braithwaite, Antony
Hung, Noelyn
Slatter, Tania L.
author_facet Jesus, Alexandra N. Boix De
Taha, Ahmad
Wang, David
Mehta, Paulomi M.
Mehta, Sunali
Reily-Bell, Ashley
Lekamlage, Sasini Polwatta
Saraiva, Adriana Machado
Tahmeedzaman, Tahmeed
Ziad, Fouzia
Thotathil, Ziad
Gan, Peter Y. C.
Royds, Janice
Braithwaite, Antony
Hung, Noelyn
Slatter, Tania L.
author_sort Jesus, Alexandra N. Boix De
collection PubMed
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. Δ133p53β mRNA expression was measured in lung, breast, melanoma, colorectal metastases and, where available, the matched primary tumor. The presence of Δ133p53β expression was associated with the time for the primary tumor to metastasize and overall survival once the tumor was detected in the brain. Δ133p53β 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 Δ133p53β expressed were associated with a reduced time for the primary tumor to metastasize to the brain compared with tumors with no Δ133p53β 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.
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spelling pubmed-98664252023-01-22 Increased Expression of the Δ133p53β Isoform Enhances Brain Metastasis Jesus, Alexandra N. Boix De Taha, Ahmad Wang, David Mehta, Paulomi M. Mehta, Sunali Reily-Bell, Ashley Lekamlage, Sasini Polwatta Saraiva, Adriana Machado Tahmeedzaman, Tahmeed Ziad, Fouzia Thotathil, Ziad Gan, Peter Y. C. Royds, Janice Braithwaite, Antony Hung, Noelyn Slatter, Tania L. Int J Mol Sci Communication 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. Δ133p53β mRNA expression was measured in lung, breast, melanoma, colorectal metastases and, where available, the matched primary tumor. The presence of Δ133p53β expression was associated with the time for the primary tumor to metastasize and overall survival once the tumor was detected in the brain. Δ133p53β 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 Δ133p53β expressed were associated with a reduced time for the primary tumor to metastasize to the brain compared with tumors with no Δ133p53β 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. MDPI 2023-01-09 /pmc/articles/PMC9866425/ /pubmed/36674782 http://dx.doi.org/10.3390/ijms24021267 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Jesus, Alexandra N. Boix De
Taha, Ahmad
Wang, David
Mehta, Paulomi M.
Mehta, Sunali
Reily-Bell, Ashley
Lekamlage, Sasini Polwatta
Saraiva, Adriana Machado
Tahmeedzaman, Tahmeed
Ziad, Fouzia
Thotathil, Ziad
Gan, Peter Y. C.
Royds, Janice
Braithwaite, Antony
Hung, Noelyn
Slatter, Tania L.
Increased Expression of the Δ133p53β Isoform Enhances Brain Metastasis
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 Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866425/
https://www.ncbi.nlm.nih.gov/pubmed/36674782
http://dx.doi.org/10.3390/ijms24021267
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