Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells

TY - JOUR

T1 - Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells

AU - Arsic, Nikola

AU - Slatter, Tania

AU - Gadea, Gilles

AU - Villain, Etienne

AU - Fournet, Aurelie

AU - Kazantseva, Marina

AU - Allemand, Frédéric

AU - Sibille, Nathalie

AU - Seveno, Martial

AU - de Rossi, Sylvain

AU - Mehta, Sunali

AU - Urbach, Serge

AU - Bourdon, Jean Christophe

AU - Bernado, Pau

AU - Kajava, Andrey V.

AU - Braithwaite, Antony

AU - Roux, Pierre

N1 - Funding Information: This paper was supported by grant from INCa no. 2017-169, no. CNRS: 157944 N.A., P.R. and A.K. are supported by CNRS. A.W.B., T.S., S.M. and M.K. are supported by grants from the Health Research Council and Royal Society of New Zealand. P.R. is supported by INSERM. We acknowledge the imaging facility MRI, member of the national infrastructure France-BioImaging infrastructure supported by the French National Research Agency (ANR-10-INBS-04, «Investments for the future»). We thank Véronique Gire and Philippe Fort (CRBM, CNRS, Montpellier) for helpful discussions. Mass spectrometry experiments were carried out using the facilities of the Montpellier Proteomics Platform (PPM, BioCampus Montpellier). We acknowledge Maurice Wilkins Centre for Molecular Biodiscovery for RNAseq funding. Publisher Copyright: © 2021, The Author(s).

PY - 2021/9/15

Y1 - 2021/9/15

N2 - The p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies. The Δ133p53β aggregation depends on association with interacting partners including p63 family members or the CCT chaperone complex. Depletion of the CCT complex promotes accumulation of Δ133p53β aggregates and loss of Δ133p53β dependent cancer cell invasion. In contrast, association with p63 family members recruits Δ133p53β from aggregates increasing its intracellular mobility. Our study reveals novel mechanisms of cancer progression for p53 isoforms which are regulated through sequestration in aggregates and recruitment upon association with specific partners like p63 isoforms or CCT chaperone complex, that critically influence cancer cell features like EMT, migration and invasion.

AB - The p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies. The Δ133p53β aggregation depends on association with interacting partners including p63 family members or the CCT chaperone complex. Depletion of the CCT complex promotes accumulation of Δ133p53β aggregates and loss of Δ133p53β dependent cancer cell invasion. In contrast, association with p63 family members recruits Δ133p53β from aggregates increasing its intracellular mobility. Our study reveals novel mechanisms of cancer progression for p53 isoforms which are regulated through sequestration in aggregates and recruitment upon association with specific partners like p63 isoforms or CCT chaperone complex, that critically influence cancer cell features like EMT, migration and invasion.

KW - Cancer

KW - Cell Biology

UR - https://www.scopus.com/pages/publications/85115239726

U2 - 10.1038/s41467-021-25550-2

DO - 10.1038/s41467-021-25550-2

M3 - Article

C2 - 34526502

AN - SCOPUS:85115239726

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

M1 - 5463

ER -