TP53 drives invasion through expression of its Δ133p53β variant

Gilles Gadea; Nikola Arsic; Kenneth Fernandes; Alexandra Diot; Sébastien M. Joruiz; Samer Abdallah; Valerie Meuray; Stéphanie Vinot; Christelle Anguille; Judit Remenyi; Marie P. Khoury; Philip R. Quinlan; Colin A. Purdie; Lee B. Jordan; Frances V. Fuller-Pace; Marion De Toledo; Maïlys Cren; Alastair M. Thompson; Jean Christophe Bourdon; Pierre Roux

doi:10.7554/eLife.14734

TP53 drives invasion through expression of its Δ133p53β variant

Gilles Gadea, Nikola Arsic, Kenneth Fernandes, Alexandra Diot, Sébastien M. Joruiz, Samer Abdallah, Valerie Meuray, Stéphanie Vinot, Christelle Anguille, Judit Remenyi, Marie P. Khoury, Philip R. Quinlan, Colin A. Purdie, Lee B. Jordan, Frances V. Fuller-Pace, Marion De Toledo, Maïlys Cren, Alastair M. Thompson, Jean Christophe Bourdon, Pierre Roux

Surgical Oncology

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41 Scopus citations

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.

Original language	English (US)
Article number	e14734
Journal	eLife
Volume	5
Issue number	September2016
DOIs	https://doi.org/10.7554/eLife.14734
State	Published - Sep 2016

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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Gadea, G., Arsic, N., Fernandes, K., Diot, A., Joruiz, S. M., Abdallah, S., Meuray, V., Vinot, S., Anguille, C., Remenyi, J., Khoury, M. P., Quinlan, P. R., Purdie, C. A., Jordan, L. B., Fuller-Pace, F. V., De Toledo, M., Cren, M., Thompson, A. M., Bourdon, J. C., & Roux, P. (2016). TP53 drives invasion through expression of its Δ133p53β variant. eLife, 5(September2016), Article e14734. https://doi.org/10.7554/eLife.14734

Gadea, G, Arsic, N, Fernandes, K, Diot, A, Joruiz, SM, Abdallah, S, Meuray, V, Vinot, S, Anguille, C, Remenyi, J, Khoury, MP, Quinlan, PR, Purdie, CA, Jordan, LB, Fuller-Pace, FV, De Toledo, M, Cren, M, Thompson, AM, Bourdon, JC & Roux, P 2016, 'TP53 drives invasion through expression of its Δ133p53β variant', eLife, vol. 5, no. September2016, e14734. https://doi.org/10.7554/eLife.14734

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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.",

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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

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TP53 drives invasion through expression of its Δ133p53β variant

Abstract

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