The Δ133p53 Isoform and Its Mouse Analogue Δ122p53 Promote Invasion and Metastasis Involving Pro-Inflammatory Molecules interleukin-6 and CCL2

Oncogene. 2016 Sep 22;35(38):4981-9. doi: 10.1038/onc.2016.45. Epub 2016 Mar 21.


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 Δ133p53 isoform using our mouse model of Δ133p53 (Δ122p53). Here, we report that tumours from Δ122p53 homozygous mice show evidence of invasion and metastasis and that Δ122p53 promotes migration though a 3-dimensional collagen matrix. We also show that Δ122p53 and Δ133p53 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 Δ122p53 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 Δ122p53 (and Δ133p53) 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 Δ133p53-expressing tumours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Chemokine CCL2 / genetics*
  • Humans
  • Interleukin-6 / genetics*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Melanoma, Experimental / genetics*
  • Melanoma, Experimental / pathology
  • Mice
  • Mutation
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis
  • Protein Isoforms
  • Tumor Suppressor Protein p53 / genetics*


  • CCL2 protein, human
  • Chemokine CCL2
  • Interleukin-6
  • Protein Isoforms
  • Tumor Suppressor Protein p53