Increased Expression of the Δ133p53β Isoform Enhances Brain Metastasis

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...

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Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:International Journal of Molecular Sciences
Subjects:
p53 isoform
Δ133p53β
brain
metastasis
time to metastasis
receptor recycling
Online Access:https://www.mdpi.com/1422-0067/24/2/1267
Description
Summary: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.
ISSN:1661-6596
1422-0067

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