TY - JOUR
T1 - TP53 drives invasion through expression of its ∆133p53β variant
AU - Gadea, Gilles
AU - Arsic, Nikola
AU - Fernandes, Kenneth
AU - Diot, Alexandra
AU - Joruiz, Sébastien M.
AU - Abdallah, Samer
AU - Meuray, Valerie
AU - Vinot, Stéphanie
AU - Anguille, Christelle
AU - Remenyi, Judit
AU - Khoury, Marie P.
AU - Quinlan, Philip R.
AU - Purdie, Colin A.
AU - Jordan, Lee B.
AU - Fuller-Pace, Frances V.
AU - de Toledo, Marion
AU - Cren, Maïlys
AU - Thompson, Alastair M.
AU - Bourdon, Jean-Christophe
AU - Roux , Pierre
N1 - The Tayside Tissue Bank is supported by Breast Cancer Campaign, Cancer Research UK (CRUK) and by NHS Tayside through the Chief Scientist Office and Health Sciences Scotland (formerly the Scottish Academic Health Science Collaboration, AHSC). JC Bourdon is a fellow of Breast Cancer Now (2012MaySF127). K Fernandes, J Remenyi, P Quinlan and AM Thompson are supported by Breast Cancer Campaign (BCC: 2010NovPR50, BCC, 2010NovPR16 and BCC, TB2009DUN, respectively). M Khoury was supported by the ‘Association pour la Recherche contre le Cancer’ (contract AO/3/5099). G Gadea, N Arsic and P Roux are supported by CNRS and INSERM.
PY - 2016/9/15
Y1 - 2016/9/15
N2 - 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.
AB - 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.
U2 - 10.7554/eLife.14734
DO - 10.7554/eLife.14734
M3 - Article
C2 - 27630122
SN - 2050-084X
VL - 5
SP - 1
EP - 26
JO - eLife
JF - eLife
M1 - e14734
ER -