The Delta133p53 isoform and its mouse analogue Delta122p53 promote invasion and metastasis involving pro-inflammatory molecules interleukin-6 and CCL2
A number of naturally occurring isoforms of the tumour suppressor protein p53 have been discovered, which appear to have differing roles in tumour prevention or promotion. We are investigating the tumour-promoting activities of the Delta133p53 isoform using our mouse model of Delta133p53 (Delta122p53). Here, we report that tumours from Delta122p53 homozygous mice show evidence of invasion and metastasis and that Delta122p53 promotes migration though a 3-dimensional collagen matrix. We also show that Delta122p53 and Delta133p53 promote cell migration in scratch wound and Transwell assays, similar to the 'gain-of-function' phenotypes seen with mutant p53. Using the well-defined B16 mouse melanoma metastatic model, we show that Delta122p53 leads to faster generation of lung metastases. The increased migratory phenotypes are dependent on secreted factors, including the cytokine interleukin-6 and the chemokine CCL2. We propose that Delta122p53 (and Delta133p53) acts in a similar manner to 'gain-of-function' mutant p53 proteins to promote migration, invasion and metastasis, which may contribute to poor survival in patients with Delta133p53-expressing tumours.
|ISBN||1476-5594 (Electronic) 0950-9232 (Linking)|
|Authors||Roth, I.; Campbell, H.; Rubio, C.; Vennin, C.; Wilson, M.; Wiles, A.; Williams, G.; Woolley, A.; Timpson, P.; Berridge, M. V.; Fleming, N.; Baird, M.; Braithwaite, A. W.;|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/26996665|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/13665|