Our research

In multicellular organisms, cells move, and they do it in a specific manner. This fundamental process obeys strict regulations that are essential for the proper occurrence of specific life features, for example embryonic development or activation of the immune defences. Dysregulated cell migration can cause major problems, such as metastasis formation, the process during which cancer cells from a primary tumour disseminate to other body sites, ultimately resulting in the patient’s death. Understanding how cancer cells become invasive and identifying the molecular processes that regulate their abnormal migration are crucial biological issues and constitute our area of research.

The p53 tumour suppressor is the most commonly mutated gene in human tumours and has attracted much attention since its discovery in 1979. Our studies are focused on the mechanisms used by tumour cells to inactivate p53 function. Despite the immense prevalence of p53 mutations in human tumours, p53 gene mutation status cannot precisely explain the acquisition of an invasive phenotype. Indeed, numerous clinical data show that p53 mutation status cannot be used as a prognostic marker of tumour progression. This suggests that mechanisms other than mutations are involved in the inhibition of p53 tumour suppressor function.

One of these mechanisms is the production of p53 variant proteins (isoforms) by alternative splicing of the gene, a process that controls the presence or absence of several p53 domains in the protein. Our team studies the p53 isoforms produced by cancer cells, the underlying molecular mechanisms of their formation and their consequences on metastatic invasion.

We analyse the role of p53 isoforms in cellular processes associated with tumour invasion: mode of migration, cellular senescence and tumour stem cell formation. A major objective is to determine whether specific isoforms are associated with tumour aggressiveness and may constitute novel therapeutic targets. In this context, we are currently identifying the cellular pathways that activate the expression of p53 isoforms during cancer invasion. We also try decoding the mechanisms by which these isoforms control cancer cell invasion through the identification of their partners and their targets.

Our in vivo studies are carried out in cells grown in 2D and also 3D culture systems that best recapitulate the tissue physiological conditions. We combine cell analysis techniques (live cell imaging, stem cell potential, mouse xenografts), human tumour sample analysis and high throughput proteomic and transcriptomic analyses.

Financements

AxLR, SATT Occitanie Méditerranée - Minalogic

Publications

2022

Reciprocal regulation of p21 and Chk1 controls the cyclin D1-RB pathway to mediate senescence onset after G2 arrest. Lossaint G, Horvat A, Gire V, Bačević K, Mrouj K, Charrier-Savournin F, Georget V, Fisher D, Dulić V. J Cell Sci. 2022 Apr 15;135(8):jcs259114. Pubmed
Regulation of Src tumor activity by its N-terminal intrinsically disordered region. Aponte E, Lafitte M, Sirvent A, Simon V, Barbery M, Fourgous E, Boublik Y, Maffei M, Armand F, Hamelin R, Pannequin J, Fort P, Pons M, Roche S. Oncogene. 2022 Feb;41(7):960-970. Pubmed

2021

Mechanisms and Regulation of Cellular Senescence. Roger L, Tomas F, Gire V. Int J Mol Sci. 2021 Dec 6;22(23):13173 Pubmed
NOPCHAP1 is a PAQosome cofactor that helps loading NOP58 on RUVBL1/2 during box C/D snoRNP biogenesis. Abel Y, Paiva ACF, Bizarro J, Chagot ME, Santo PE, Robert MC, Quinternet M, Vandermoere F, Sousa PMF, Fort P, Charpentier B, Manival X, Bandeiras TM, Bertrand E, Verheggen C. Nucleic Acids Res. 2021 Jan 25;49(2):1094-1113 Pubmed
Dependent Oncogenic Signaling of the PEAK3 Pseudo-Kinase. Ounoughene Y, Fourgous E, Boublik Y, Saland E, Guiraud N, Recher C, Urbach S, Fort P, Sarry JE, Fesquet D, Roche S. Cancers (Basel). 2021 Dec 17;13(24):6344 Pubmed
Aspartate-phobia of thermophiles as a reaction to deleterious chemical transformations. Villain E, Fort P, Kajava AV. Bioessays. 2022 Jan;44(1):e2100213 Pubmed
Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells. Arsic N, Slatter T, Gadea G, Villain E, Fournet A, Kazantseva M, Allemand F, Sibille N, Seveno M, de Rossi S, Mehta S, Urbach S, Bourdon JC, Bernado P, Kajava AV, Braithwaite A, Roux P. Nat Commun 12:5463 Pubmed
p53, A Victim of the Prion Fashion. Billant O, Friocourt G, Roux P, Voisset C. Cancers (Basel). 13(2):269 Pubmed

2019

New insights into the evolutionary conservation of the sole PIKK pseudokinase Tra1/TRRAP. Elías-Villalobos A, Fort P, Helmlinger D. Biochem Soc Trans. 2019 Dec 20;47(6):1597-1608 Pubmed
The atypical RhoU/Wrch1 Rho GTPase controls cell proliferation and apoptosis in the gut epithelium. Slaymi C, Vignal E, Crès G, Roux P, Blangy A, Raynaud P, Fort P. Biol Cell. 2019 May;111(5):121-141 Pubmed

2018

PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ. Jonik-Nowak B, Menneteau T, Fesquet D, Baldin V, Bonne-Andrea C, Méchali F, Fabre B, Boisguerin P, de Rossi S, Henriquet C, Pugnière M, Ducoux-Petit M, Burlet-Schiltz O, Lamond AI, Fort P, Boulon S, Bousquet MP, Coux O. Proc Natl Acad Sci U S A. pii: 201722299. Pubmed
SOX9 has distinct regulatory roles in alternative splicing and transcription. Girardot M, Bayet E, Maurin J, Fort P, Roux P, Raynaud P. Nucleic Acids Res. doi: 10.1093/nar/gky553. Pubmed
The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones. Maurizy C, Quinternet M, Abel Y, Verheggen C, Santo PE, Bourguet M, C F Paiva A, Bragantini B, Chagot ME, Robert MC, Abeza C, Fabre P, Fort P, Vandermoere F, M F Sousa P, Rain JC, Charpentier B, Cianférani S, Bandeiras TM, Pradet-Balade B, Manival X, Bertrand E. Nat Commun. 9(1):2093. Pubmed
∆133p53 isoform promotes tumour invasion and metastasis via interleukin-6 activation of JAK-STAT and RhoA-ROCK signalling. Campbell H, Fleming N, Roth I, Mehta S, Wiles A, Williams G, Vennin C, Arsic N, Parkin A, Pajic M, Munro F, McNoe L, Black M, McCall J, Slatter TL, Timpson P, Reddel R, Roux P, Print C, Baird MA, Braithwaite AW. Nat Commun. 9(1):254. Pubmed

2017

The Evolutionary Landscape of Dbl-Like RhoGEF Families: Adapting Eukaryotic Cells to Environmental Signals. Fort P, Blangy A. Genome Biol Evol. 9:1471-1486. Pubmed
Heterogeneity in sarcoma cell lines reveals enhanced motility of tetraploid versus diploid cells. Jemaà M, Abdallah S, Lledo G, Perrot G, Lesluyes T, Teyssier C, Roux P, van Dijk J, Chibon F, Abrieu A, Morin N. 14291 Pubmed

Binding site density enables paralog-specific activity of SLM2 and Sam68 proteins in Neurexin2 AS4 splicing control. Danilenko M, Dalgliesh C, Pagliarini V, Naro C, Ehrmann I, Feracci M, Kheirollahi-Chadegani M, Tyson-Capper A, Clowry GJ, Fort P, Dominguez C, Sette C, Elliott DJ. Nucleic Acids Res. pii: gkw1277. Pubmed
The p53 isoform delta133p53ß regulates cancer cell apoptosis in a RhoB-dependent manner. Arsic N, Ho-Pun-Cheung A, Evelyne C, Assenat E, Jarlier M, Anguille C, Colard M, Pezet M, Roux P, Gadea G. PLoS One. 12:e0172125. Pubmed

2016

TP53 drives invasion through expression of its Δ133p53β variant. 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. 5: e14734. Pubmed
A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior. Ehrmann I, Gazzara MR, Pagliarini V, Dalgliesh C, Kheirollahi-Chadegani M, Xu Y, Cesari E, Danilenko M, Maclennan M, Lowdon K, Vogel T, Keskivali-Bond P, Wells S, Cater H, Fort P, Santibanez-Koref M, Middei S, Sette C, Clowry GJ, Barash Y, Cunningham MO, Elliott DJ. Cell Rep. 17:3269-3280. Pubmed
STARs in the CNS. Ehrmann I, Fort P, Elliott DJ. Biochem Soc Trans. 44:1066-72. Pubmed
High chlorpyrifos resistance in Culex pipiens mosquitoes: strong synergy between resistance genes. Alout H, Labbé P, Berthomieu A, Makoundou P, Fort P, Pasteur N, Weill M. Heredity (Edinb). 116:224-31. Pubmed

2015

Greatwall promotes cell transformation by hyperactivating AKT in human malignancies. Vera J, Lartigue L, Vigneron S, Gadea G, Gire V, Del Rio M, Soubeyran I, Chibon F, Lorca T, Castro A. 4:e10115. Pubmed
Neural differentiation modulates the vertebrate brain specific splicing program. Madgwick A, Fort P, Hanson PS, Thibault P, Gaudreau MC, Lutfalla G, Möröy T, Abou Elela S, Chaudhry B, Elliott DJ, Morris CM, Venables JP. PLoS One. 10:e0125998. Pubmed
Senescence from G2 arrest, revisited. Gire V, Dulic V. Cell Cycle. 14:297-304. Pubmed
Evolution of proteasome regulators in eukaryotes. Fort P, Kajava AV, Delsuc F, Coux O. Genome Biol Evol. 7:1363-79. Pubmed
Atypical RhoV and RhoU GTPases control development of the neural crest. Faure S, Fort P. Small GTPases. 6:174-7. Pubmed
Stable coexistence of incompatible Wolbachia along a narrow contact zone in mosquito field populations. Atyame CM, Labbé P, Rousset F, Beji M, Makoundou P, Duron O, Dumas E, Pasteur N, Bouattour A, Fort P, Weill M. Mol Ecol. 24:508-21. Pubmed
The p53 isoform Δ133p53β promotes cancer stem cell potential. Arsic N, Gadea G, Lagerqvist EL, Busson M, Cahuzac N, Brock C, Hollande F, Gire V, Pannequin J, Roux P. Stem Cell Reports. 4:531-40. Pubmed

2014

Postprandial triglyceride-rich lipoproteins promote invasion of human coronary artery smooth muscle cells in a fatty-acid manner through PI3k-Rac1-JNK signaling. Varela LM, Bermúdez B, Ortega-Gómez A, López S, Sánchez R, Villar J, Anguille C, Muriana FJ, Roux P, Abia R. Mol Nutr Food Res. 58:1349-64. Pubmed
Antagonistic functions of LMNA isoforms in energy expenditure and lifespan. Lopez-Mejia IC, de Toledo M, Chavey C, Lapasset L, Cavelier P, Lopez-Herrera C, Chebli K, Fort P, Beranger G, Fajas L, Amri EZ, Casas F, Tazi J. EMBO Rep. 15:529-39 Pubmed
PleiotRHOpic: Rho pathways are essential for all stages of Neural Crest development. Fort P, Théveneau E. Small GTPases. 5:e27975. Pubmed
Wolbachia divergence and the evolution of cytoplasmic incompatibility in Culex pipiens. Atyame CM, Labbé P, Dumas E, Milesi P, Charlat S, Fort P, Weill M. PLoS One. 9:e87336. Pubmed

2013

The tissue-specific RNA binding protein T-STAR controls regional splicing patterns of neurexin pre-mRNAs in the brain. Ehrmann I, Dalgliesh C, Liu Y, Danilenko M, Crosier M, Overman L, Arthur HM, Lindsay S, Clowry GJ, Venables JP, Fort P, Elliott DJ. PLoS Genet. 2013 Apr;9(4):e1003474. Pubmed
Applying ecological and evolutionary theory to cancer: a long and winding road. Thomas F, Fisher D, Fort P, Marie JP, Daoust S, Roche B, Grunau C, Cosseau C, Mitta G, Baghdiguian S, Rousset F, Lassus P, Assenat E, Grégoire D, Missé D, Lorz A, Billy F, Vainchenker W, Delhommeau F, Koscielny S, Itzykson R, Tang R, Fava F, Ballesta A, Lepoutre T, Krasinska L, Dulic V, Raynaud P, Blache P, Quittau-Prevostel C, Vignal E, Trauchessec H, Perthame B, Clairambault J, Volpert V, Solary E, Hibner U, Hochberg ME. Evol Appl. 2013 Jan;6(1):1-10. Pubmed
Eroded human telomeres are more prone to remain uncapped and to trigger a G2 checkpoint response. Jullien L, Mestre M, Roux P, Gire V. Nucleic Acids Res. 41(2):900-11. Pubmed
MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation. Venables JP, Lapasset L, Gadea G, Fort P, Klinck R, Irimia M, Vignal E, Thibault P, Prinos P, Chabot B, Abou Elela S, Roux P, Lemaitre JM, Tazi J. Nat Commun. 2013;4:2480. Pubmed
Targeting the Dbl and dock-family RhoGEFs: a yeast-based assay to identify cell-active inhibitors of Rho-controlled pathways. Blangy A, Fort P. Enzymes. 2013;33 Pt A:169-91. Pubmed

2012

Tissue-specific alternative splicing of Tak1 is conserved in deuterostomes. Venables JP, Vignal E, Baghdiguian S, Fort P, Tazi J. Mol Biol Evol. 2012 Jan;29(1):261-9. Pubmed
Fossil rhabdoviral sequences integrated into arthropod genomes: ontogeny, evolution, and potential functionality. Fort P, Albertini A, Van-Hua A, Berthomieu A, Roche S, Delsuc F, Pasteur N, Capy P, Gaudin Y, Weill M. Mol Biol Evol. 2012 Jan;29(1):381-90. Pubmed
Novel AChE inhibitors for sustainable insecticide resistance management. Alout H, Labbé P, Berthomieu A, Djogbénou L, Leonetti JP, Fort P, Weill M. PLoS One. 2012;7(10):e47125. Pubmed
Matrix-bound PAI-1 supports cell blebbing via RhoA/ROCK1 signaling. Cartier-Michaud A, Malo M, Charrière-Bertrand C, Gadea G, Anguille C, Supiramaniam A, Lesne A, Delaplace F, Hutzler G, Roux P, Lawrence DA, Barlovatz-Meimon G. PLoS One. 2012;7(2):e32204. Pubmed
ZNF217 is a marker of poor prognosis in breast cancer that drives epithelial-mesenchymal transition and invasion. Vendrell JA, Thollet A, Nguyen NT, Ghayad SE, Vinot S, Bièche I, Grisard E, Josserand V, Coll JL, Roux P, Corbo L, Treilleux I, Rimokh R, Cohen PA. Cancer Res. 2012 Jul 15;72(14):3593-606. Pubmed
Cooperative anti-invasive effect of Cdc42/Rac1 activation and ROCK inhibition in SW620 colorectal cancer cells with elevated blebbing activity. de Toledo M, Anguille C, Roger L, Roux P, Gadea G. PLoS One. 7(11):e48344. Pubmed
Using a modified yeast two-hybrid system to screen for chemical GEF inhibitors. Blangy A, Fort P. Methods Mol Biol. 2012;928:81-95. Pubmed

2011

Multiple Wolbachia determinants control the evolution of cytoplasmic incompatibilities in Culex pipiens mosquito populations. Atyame CM, Duron O, Tortosa P, Pasteur N, Fort P, Weill M. Mol Ecol. 2011 Jan;20(2):286-98. Pubmed
MiniSOX9, a dominant-negative variant in colon cancer cells. Abdel-Samad R, Zalzali H, Rammah C, Giraud J, Naudin C, Dupasquier S, Poulat F, Boizet-Bonhoure B, Lumbroso S, Mouzat K, Bonnans C, Pignodel C, Raynaud P, Fort P, Quittau-Prévostel C, Blache P. Oncogene. 2011 Jun 2;30(22):2493-503. Pubmed
Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling. Yano T, Yamazaki Y, Adachi M, Okawa K, Fort P, Uji M, Tsukita S, Tsukita S. J Cell Biol. 2011 Apr 18;193(2):319-32. Pubmed
Activity of the RhoU/Wrch1 GTPase is critical for cranial neural crest cell migration. Fort P, Guémar L, Vignal E, Morin N, Notarnicola C, de Santa Barbara P, Faure S. Dev Biol. 350(2):451-63. Pubmed

2010

What makes cells move: requirements and obstacles for spontaneous cell motility. Binamé F, Pawlak G, Roux P, Hibner U. Mol Biosyst. 6(4):648-61. Pubmed
Gain of oncogenic function of p53 mutants regulates E-cadherin expression uncoupled from cell invasion in colon cancer cells. Roger L, Jullien L, Gire V, Roux P. J Cell Sci. 123(Pt 8):1295-305. Pubmed

2009

TC10 controls human myofibril organization and is activated by the sarcomeric RhoGEF obscurin. Coisy-Quivy M, Touzet O, Bourret A, Hipskind RA, Mercier J, Fort P, Philips A. J Cell Sci. 2009 Apr 1;122(Pt 7):947-56. Pubmed
A cell active chemical GEF inhibitor selectively targets the Trio/RhoG/Rac1 signaling pathway. Bouquier N, Vignal E, Charrasse S, Weill M, Schmidt S, Léonetti JP, Blangy A, Fort P. Chem Biol. 2009 Jun 26;16(6):657-66. Pubmed

2008

Analysis of cell migration and its regulation by Rho GTPases and p53 in a three-dimensional environment. Vinot S, Anguille C, de Toledo M, Gadea G, Roux P. Methods Enzymol. 439:413-24. Pubmed
Dynamic expression patterns of RhoV/Chp and RhoU/Wrch during chicken embryonic development. Notarnicola C, Le Guen L, Fort P, Faure S, de Santa Barbara P.Dev Dyn. 2008 Apr;237(4):1165-71. Pubmed

Team R&D : Dynamics of cell invasion in cancer

Pierre ROUX

Chef d’équipe (Chercheur DR2)

Team Members

Nikola ARSIC (IR-Recherche) +33 (0)4 34 35 95 12
Veronique GIRE (CRCN) +33 (0)4 34 35 95 13
Pierre ROUX Chef d'équipe (Chercheur DR2) +33 (0)4 34 35 95 12

Contact our team

Remplacez le nom et l’adresse ci-dessus par celui du membre à contacter
prenom.nom@crbm.cnrs.fr

AxLR, SATT Occitanie Méditerranée - Minalogic

NOS PUBLICATIONS

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

Arsic N, Slatter T, Gadea G, Villain E, Fournet A, Kazantseva M, Allemand F, Sibille N, Seveno M, de Rossi S, Mehta S, Urbach S, Bourdon JC, Bernado P, Kajava AV, Braithwaite A, Roux P.

Nat Commun. 2021 Sep 15;12(1):5463.

Pubmed

∆133p53 isoform promotes tumour invasion and metastasis via interleukin-6 activation of JAK-STAT and RhoA-ROCK signalling.

Campbell H, Fleming N, Roth I, Mehta S, Wiles A, Williams G, Vennin C, Arsic N, Parkin A, Pajic M, Munro F, McNoe L, Black M, McCall J, Slatter TL, Timpson P, Reddel R, Roux P, Print C, Baird MA, Braithwaite AW.