Effect of p53 and its N-terminally truncated isoform, Δ40p53, on breast cancer migration and invasion

Breast cancer is the most diagnosed malignancy in women, with over half a million women dying from this disease each year. In our previous studies, Delta 40p53, an N-terminally truncated p53 isoform, was found to be upregulated in breast cancers, and a high Delta 40p53 : p53 alpha ratio was linked with worse disease-free survival. Although p53 alpha inhibits cancer migration and invasion, little is known about the role of Delta 40p53 in regulating these metastasis-related processes and its role in contributing to worse prognosis. The aim of this study was to assess the role of Delta 40p53 in breast cancer migration and invasion. A relationship between Delta 40p53 and gene expression profiles was identified in oestrogen-receptor-positive breast cancer specimens. To further evaluate the role of Delta 40p53 in oestrogen-receptor-positive breast cancer, MCF-7 and ZR75-1 cell lines were transduced to knockdown p53 alpha or Delta 40p53 and overexpress Delta 40p53. Proliferation, migration and invasion were assessed in the transduced sublines, and gene expression was assessed through RNA-sequencing and validated by reverse-transcription quantitative PCR. Knockdown of both p53 alpha and Delta 40p53 resulted in increased proliferation, whereas overexpression of Delta 40p53 reduced proliferation rates. p53 alpha knockdown was also associated with increased cell mobility. Delta 40p53 overexpression reduced both migratory and invasive properties of the transduced cells. Phenotypic findings are supported by gene expression data, including differential expression of LRG1, HYOU1, UBE2QL1, SERPINA5 and PCDH7. Taken together, these results suggest that, at the basal level, Delta 40p53 works similarly to p53 alpha in suppressing cellular mobility and proliferation, although the role of Delta 40p53 may be cell context-specific.

Automated summary

This study aimed to evaluate the role of Delta 40p53 in breast cancer migration and invasion, finding an association between Delta 40p53 and gene expression profiles. Knockdown of both p53 alpha and Delta 40p53 resulted in increased proliferation, while overexpression of Delta 40p53 reduced proliferation rates and decreased migratory and invasive properties of the cells. These results suggest that at a basal level, Delta 40p53 works similarly to p53 alpha in suppressing cellular mobility and proliferation.