title: The Δ133p53 isoform and its mouse analogue Δ122p53 promote invasion and metastasis involving pro-inflammatory molecules interleukin-6 and CCL2.
abstract: 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.
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.|Maurice Wilkins Centre for Molecular Biodiscovery, School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: I
authors.initials: I
authors.lastname: Roth
authors.affiliation: Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Campbell
authors.affiliation: Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Rubio
authors.affiliation: The Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Vennin
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: M
authors.initials: M
authors.lastname: Wilson
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: A
authors.initials: A
authors.lastname: Wiles
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: G
authors.initials: G
authors.lastname: Williams
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: A
authors.initials: A
authors.lastname: Woolley
authors.affiliation: The Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Timpson
authors.affiliation: Malaghan Institute for Medical Research, Wellington, New Zealand.
authors.forename: M V
authors.initials: MV
authors.lastname: Berridge
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: N
authors.initials: N
authors.lastname: Fleming
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.|Maurice Wilkins Centre for Molecular Biodiscovery, School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: M
authors.initials: M
authors.lastname: Baird
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.|Maurice Wilkins Centre for Molecular Biodiscovery, School of Biological Sciences, University of Auckland, Auckland, New Zealand.|Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: A W
authors.initials: AW
authors.lastname: Braithwaite
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D018932:Chemokine CCL2 / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D008546:Melanoma, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53