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.

The present study aimed to synthesize thiophene carboxamide derivatives, which are considered biomimetics of the anticancer medication Combretastatin A-4 (CA-4), and compare the similarity in the polar surface area (PSA) between the novel series and CA-4. Our results showed that the PSA of the most synthesized structures was biomimetic to CA-4, and similar chemical and biological properties were observed against Hep3B cancer cell line. Among the synthesized series 2b and 2e compounds were the most active molecules on Hep3B (IC₅₀ = 5.46 and 12.58 µM, respectively). The 3D results revealed that both 2b and 2e structures confuse the surface of Hep3B cancer cell lines’ spheroid formation and force these cells to aggregate into a globular-shaped spheroid. The 2b and 2e showed a comparable interaction pattern to that observed for CA-4 and colchicine within the tubulin-colchicine-binding pocket. The thiophene ring, due to holding a high aromaticity character, participated critically in that observed interaction profile and showed additional advanced interactions over CA-4. The 2b and 2e tubulin complexes showed optimal dynamics trajectories within a time scale of 100 ns at 300 K temperature, which asserts their high stability and compactness. Together, these findings revealed the biomimetic role of 2b and 2e compounds in CA-4 in preventing cancer progression.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Mohamed Jemaà1, 2, Samer Abdallah1, 2, Gwendaline Lledo1, 2, Gaelle Perrot3, Tom Lesluyes3, Catherine Teyssier4, Pierre Roux1, 2, Juliette van Dijk1, 2, Frederic Chibon3, 5, Ariane Abrieu1, 2, Nathalie Morin1, 2 1Universités de Montpellier, 34293 Montpellier, France 2CRBM, CNRS, UMR 5237, 34293 Montpellier, France 3INSERM U1218, Bergonié Cancer Institute, F-33076 Bordeaux, France 4U1194 INSERM, IRCM, 34298 Montpellier, France 5Department of Pathology, Bergonié Cancer Institute, F-33076 Bordeaux, France Correspondence to: Abrieu Ariane, email: ariane.abrieu@crbm.cnrs.fr Morin Nathalie, email: nathalie.morin@crbm.cnrs.fr Keywords: sarcoma, CINSARC, mitosis, motility, diploid/tetraploid Received: May 13, 2016 Accepted: November 30, 2016 Published: December 27, 2016