Increased Expression of the 133p53 Isoform Enhances Brain Metastasis

The delta 133p53 beta 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 delta 133p53 beta contributed to some of the most aggressive tumors that had metasta-sized to the brain. delta 133p53 beta mRNA expression was measured in lung, breast, melanoma, colorectal metastases and, where available, the matched primary tumor. The presence of delta 133p53 beta expression was associated with the time for the primary tumor to metastasize and overall survival once the tumor was detected in the brain. delta 133p53 beta 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 delta 133p53 beta expressed were associated with a reduced time for the primary tumor to metastasize to the brain compared with tumors with no delta 133p53 beta expression. In-vitro-based analyses in delta 133p53 beta-expressing cells showed increased cancer-promoting proteins on the cell surface and increased downstream p-AKT and p-MAPK signaling. delta 133p53 beta-expressing cells also invaded more readily across a mock blood-brain barrier. Together these data suggested that delta 133p53 beta contributes to brain metastases by making cells more likely to invade the brain.