TP53 drives invasion through expression of its Δ133p53β variant
- CNRS, Centre de Recherche de Biochimie Macromoléculaire de Montpellier, France
- University of Dundee, United Kingdom
- Université Montpellier, France
Abstract
TP53 is conventionally thought to prevent cancer formation and progression to metastasis, while mutant TP53 has transforming activities. However, in the clinic, TP53 mutation status does not accurately predict cancer progression. Here we report, based on clinical analysis corroborated with experimental data, that the p53 isoform Δ133p53β promotes cancer cell invasion, regardless of TP53 mutation status. Δ133p53β increases risk of cancer recurrence and death in breast cancer patients. Furthermore Δ133p53β is critical to define invasiveness in a panel of breast and colon cell lines, expressing WT or mutant TP53. Endogenous mutant Δ133p53β depletion prevents invasiveness without affecting mutant full-length p53 protein expression. Mechanistically WT and mutant Δ133p53β induces EMT. Our findings provide explanations to 2 long-lasting and important clinical conundrums: how WT TP53 can promote cancer cell invasion and reciprocally why mutant TP53 gene does not systematically induce cancer progression.
Article and author information
Author details
Frances V Fuller-Pace
Funding
Breast Cancer Campaign (2012MaySF127)
- Jean-Christophe Bourdon
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Joaquín M Espinosa, University of Colorado School of Medicine, United States
Ethics
Human subjects: Samples were examined following Local Research EthicsCommittee approval under delegated authority by the Tayside Tissue Bank(www.taysidetissuebank.org).
Version history
- Received: January 29, 2016
- Accepted: September 13, 2016
- Accepted Manuscript published: September 15, 2016 (version 1)
- Version of Record published: October 17, 2016 (version 2)
- Version of Record updated: March 30, 2017 (version 3)
Copyright
© 2016, Gadea et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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TP53 drives invasion through expression of its Δ133p53β variant
eLife 5:e14734.
https://doi.org/10.7554/eLife.14734
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