CONTACT

Patrick MEHLEN
patrick.mehlen
@lyon.unicancer.fr

+33 (0)4 78 78 28 70

Cheney B - 5th floor
Centre Léon Bérard

MEHLEN Patrick

Team Director

patrick.mehlen@lyon.unicancer.fr

BERNET Agnès

Professor UCBL1
agnes.bernet@lyon.unicancer.fr

PARADISI Andrea

CRN CNRS
andrea.paradisi@lyon.unicancer.fr

RAMA Nicolas
Researcher CLB

nicolas.rama@lyon.unicancer.fr

MEURETTE Olivier

Professor (MCU) 

olivier.meurette@lyon.unicancer.fr

 

FOMBONNE Joanna

Professor (MCU)
joanna.fombonne@lyon.unicancer.fr

GIBERT Benjamin

CRN CNRS
benjamin.gibert@lyon.unicancer.fr

ROCHE Colette

CRN INSERM

Colette.roche@inserm.fr

HALFON-DOMENECH Carine

MD - PhD (MCU-PH UCBL1)
carine.halfondomenech@ihope.fr

SUNDERMANN Lena

Post doc

Lena.sundermann@lyon.unicancer.fr

JASMIN Melissa-Marie

Post doc

MelissaMarie.jasmin@lyon.unicancer.fr


FATTET Laurent
Post doc
lfattet@ucsd.edu

PATTE Céline

CLB Technician
celine.patte@lyon.unicancer.fr

BOSCH Sylvie

Co-technician CNRS
sylvie.bosch@lyon.unicancer.fr

CHANAL-GUIX Catherine

CNRS Technician
catherine.guix@lyon.unicancer.fr

RADKOVA Kristina

UCBL IE

kristina.radkova@lyon.unicancer.fr

BLANC Sarah

HCL Technician

Sarah.blanc@lyon.unicacner.fr

MANCEAU Ambroise

PhD Student
ambroise.manceau@lyon.unicancer.fr

NEURURER Verena

PhD Student
verena.neururer@lyon.unicancer.fr

REDAVID Anna-Rita

PhD Student

annarita.redavid@lyon.unicancer.fr

 

RICHAUD Mathieu

PhD Student
mathieu.richaud@lyon.unicancer.fr

SCHOTT Thomas

PhD Student

thomas.schott@lyon.unicacner.fr

SUN Yan

PhD Student

Yan.sun@lyon.unicancer.fr

BELLINA Mélanie

PhD Student

melanie.bellina@lyon.unicancer.fr

GERARD Laura

M2 Student

laura_292@hotmail.fr

Voir les objectifs et projets Voir les publications

Collaborators
Alain Chedotal, Jorg Stetfeld, Manuel Koch, Pan-Chyr Yang, Dale Bredesen, Jean-Luc Ferrer, Fréderic Padilla, Dan Liebl, Keqiang Ye, Mart saarma, Andreas Trump, Cedric Blanpain, Cyrus Ghajar, Enrico Giraudo, Darren Carpizo, Igor Astsaturov, Yoshinori Murakami, Fanny Mann, Olivier Ayrault, Marie Castets, Fabrice Lavial, Gabriel Ichim.

Financial support
CNRS / INSERM / Université Claude Bernard Lyon1 / Equipe Labellisée Ligue Contre Le Cancer / ANR / INCA / Fondation ARC / Investissement d’avenir Laboratoire d’Exellence : projet DEVweCAN / Institut Convergence/ Centre Léon Bérard

OBJECTIVES

The team originally proposed the dependence receptor theory. These receptors have a dual signaling ability : when bound to their ligand they induce survival pathways, whereas they induce an active signal of cell death in the absence of their ligand. The team currently works on three approaches: (1) deciphering the molecular mechanisms of dependence receptor-induced cell death; (2) characterizing new dependence receptors; (3) analizing the physiological role of these receptors in tumor progression. Finally, the team aims at transforming basic knowlegde into therapeutic approaches to restore cell death induced by these receptors in tumors.

PROJECT

Our team investigates all aspects related to dependence receptors (DR). These receptors have a dual signaling ability: in the presence of their cognate ligand they induce a survival signal, whereas they transduce an active apoptotic signal in the absence of such ligands. More than twenty such receptors have been described to date and we speculated that their activity is instrumental for embryonic development as well as for the regulation of tumorigenesis (Mehlen et al., 2011, Nat Rev Cancer).

This concept of dependence receptors arose by highlighting the importance of such receptors in developmental processes and in tumor development. We initially proposed that the dependence receptor function was important to regulate migration and localization of cells during development (for example neurons and endothelial cells) (Thibert et al., 2003, Science; Mille et al., 2009, Nature Cell Biology; Castets et al., 2009, Dev Cell). We also showed that they had a tumor suppressive function by limiting tumor cell development in the absence of their ligands (Mazelin et al., 2004, Nature; Castets et al., 2012, Nature). Beyond the fact that the loss of receptors can lead to tumor progression, we have also shown that tumoral escape can be achieved through autocrine secretion of the ligand by cancer cells (Fitamant et al., 2008, PNAS). This observation led us to propose a therapeutic strategy based on inhibiting the binding of ligands, thus restoring the pro-apoptotic function of dependence receptors (Delloye-Bourgeois et al., 2009a, JEM; Delloye-Bourgeois et al., 2009b, JNCI; Bouzas-Rodriguez et al., 2010, JCI). 


An antibody blocking the interaction between Netrin-1 and its dependence receptors was preclinically developed (Grandin et al., Cancer Cell 2016) and has been tested in patients with advanced cancer since 2017 as part of a phase 1 trial with very encouraging clinical results

 

Today, the overall project of the team members has two facets:

1) the deepening of knowledge on molecular mechanisms downstream of these receptors, and thus, better understand of their implications on tumor progression.

2) aims to support the translation of the research observation to clinical trials.

PUBLICATIONS

2019

Cancer-associated fibroblasts produce Netrin-1 to control cancer cell plasticity. Sung PJ, Rama N, Imbach J, Fiore S, Ducarouge B, Neves D, Chen HW, Bernard D, Yang PC, Bernet A, Depil S, Mehlen P. Cancer Res. 2019 May 14. pii: canres.2952.2018. doi: 10.1158/0008-5472.CAN-18-2952.

2018

Ultrasound molecular imaging as a non-invasive companion diagnostic for netrin-1 interference therapy in breast cancer. Wischhusen J, Wilson KE, Delcros JG, Molina-Peña R, Gibert B, Jiang S, Ngo J, Goldschneider D, Mehlen P, Willmann JK, Padilla F. Theranostics. 2018 Oct 6;8(18):5126-5142. doi: 10.7150/thno.27221. 

Dependence receptors - the dark side awakens. Negulescu AM, Mehlen P. FEBS J. 2018 Nov;285(21):3909-3924. doi: 10.1111/febs.14507. 

The Proto-oncogene c-Kit Inhibits Tumor Growth by Behaving as a Dependence Receptor. Wang H, Boussouar A, Mazelin L, Tauszig-Delamasure S, Sun Y, Goldschneider D, Paradisi A, Mehlen P. Mol Cell. 2018 Nov 1;72(3):413-425.e5. doi: 10.1016/j.molcel.2018.08.040. 

Synergistic Activity of Floor-Plate- and Ventricular-Zone-Derived Netrin-1 in Spinal Cord Commissural Axon Guidance.Moreno-Bravo JA, Roig Puiggros S, Mehlen P, Chédotal A. Neuron. 2019 Feb 20;101(4):625-634.e3. doi: 10.1016/j.neuron.2018.12.024. 

Notch Signaling in the Tumor Microenvironment. Meurette O, Mehlen P. Cancer Cell. 2018 Aug 14. pii: S1535-6108(18)30315-5. doi: 10.1016/j.ccell.2018.07.009. [Epub ahead of print] Review.

The dependence receptor TrkC regulates the number of sensory neurons during DRG development. Ménard M, Costechareyre C, Coelho-Aguiar JM, Jarrosson-Wuilleme L, Rama N, Blachier J, Kindbeiter K, Bozon M, Cabrera JR, Dupin E, Le Douarin N, Mehlen P, Tauszig-Delamasure S. Dev Biol. 2018 Oct 15;442(2):249-261. doi: 10.1016/j.ydbio.2018.07.022. Epub 2018 Jul 31.

The Ectodysplasin receptor EDAR acts as a tumor suppressor in melanoma by conditionally inducing cell death. Vial J, Royet A, Cassier P, Tortereau A, Dinvaut S, Maillet D, Gratadou-Hupon L, Creveaux M, Sadier A, Tondeur G, Léon S, Depaepe L, Pantalacci S, de la Fouchardière A, Micheau O, Dalle S, Laudet V, Mehlen P, Castets M. Cell Death Differ. 2018 May 31. doi: 10.1038/s41418-018-0128-1. [Epub ahead of print]

Dependence receptors - the dark side awakens. Negulescu AM, Mehlen P. FEBS J. 2018 May 18. doi: 10.1111/febs.14507. [Epub ahead of print] Review.

Hey1- and p53-dependent TrkC proapoptotic activity controls neuroblastoma growth. Ménard M, Costechareyre C, Ichim G, Blachier J, Neves D, Jarrosson-Wuilleme L, Depping R, Koster J, Saintigny P, Mehlen P, Tauszig-Delamasure S. PLoS Biol. 2018 May 11;16(5):e2002912. doi: 10.1371/journal.pbio.2002912. eCollection 2018 May.

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, Annicchiarico-Petruzzelli M, Antonov AV, Arama E, Baehrecke EH, Barlev NA, Bazan NG, Bernassola F, Bertrand MJM, Bianchi K, Blagosklonny MV, Blomgren K, Borner C, Boya P, Brenner C, Campanella M, Candi E, Carmona-Gutierrez D, Cecconi F, Chan FK, Chandel NS, Cheng EH, Chipuk JE, Cidlowski JA, Ciechanover A, Cohen GM, Conrad M, Cubillos-Ruiz JR, Czabotar PE, D'Angiolella V, Dawson TM, Dawson VL, De Laurenzi V, De Maria R, Debatin KM, DeBerardinis RJ, Deshmukh M, Di Daniele N, Di Virgilio F, Dixit VM, Dixon SJ, Duckett CS, Dynlacht BD, El-Deiry WS, Elrod JW, Fimia GM, Fulda S, García-Sáez AJ, Garg AD, Garrido C, Gavathiotis E, Golstein P, Gottlieb E, Green DR, Greene LA, Gronemeyer H, Gross A, Hajnoczky G, Hardwick JM, Harris IS, Hengartner MO, Hetz C, Ichijo H, Jäättelä M, Joseph B, Jost PJ, Juin PP, Kaiser WJ, Karin M, Kaufmann T, Kepp O, Kimchi A, Kitsis RN, Klionsky DJ, Knight RA, Kumar S, Lee SW, Lemasters JJ, Levine B, Linkermann A, Lipton SA, Lockshin RA, López-Otín C, Lowe SW, Luedde T, Lugli E, MacFarlane M, Madeo F, Malewicz M, Malorni W, Manic G, Marine JC, Martin SJ, Martinou JC, Medema JP, Mehlen P, Meier P, Melino S, Miao EA, Molkentin JD, Moll UM, Muñoz-Pinedo C, Nagata S, Nuñez G, Oberst A, Oren M, Overholtzer M, Pagano M, Panaretakis T, Pasparakis M, Penninger JM, Pereira DM, Pervaiz S, Peter ME, Piacentini M, Pinton P, Prehn JHM, Puthalakath H, Rabinovich GA, Rehm M, Rizzuto R, Rodrigues CMP, Rubinsztein DC, Rudel T, Ryan KM, Sayan E, Scorrano L, Shao F, Shi Y, Silke J, Simon HU, Sistigu A, Stockwell BR, Strasser A, Szabadkai G, Tait SWG, Tang D, Tavernarakis N, Thorburn A, Tsujimoto Y, Turk B, Vanden Berghe T, Vandenabeele P, Vander Heiden MG, Villunger A, Virgin HW, Vousden KH, Vucic D, Wagner EF, Walczak H, Wallach D, Wang Y, Wells JA, Wood W, Yuan J, Zakeri Z, Zhivotovsky B, Zitvogel L, Melino G, Kroemer G. Cell Death Differ. 2018 Mar;25(3):486-541. doi: 10.1038/s41418-017-0012-4. Epub 2018 Jan 23. Review.

Commissural neurons transgress the CNS/PNS boundary in absence of ventricular zone-derived netrin 1. Moreno-Bravo JA, Roig Puiggros S, Blockus H, Dominici C, Zelina P, Mehlen P, Chédotal A. Development. 2018 Jan 17;145(2). pii: dev159400. doi: 10.1242/dev.159400.


2017

Hepatocellular carcinoma-associated depletion of the netrin-1 receptor Uncoordinated Phenotype-5A (UNC5A) skews the hepatic unfolded protein response towards prosurvival outcomes. Barnault R, Lahlali T, Plissonnier ML, Romero-López C, Laverdure N, Ducarouge B, Rivoire M, Mehlen P, Zoulim F, Parent R. Biochem Biophys Res Commun. 2018 Jan 22;495(4):2425-2431. doi: 10.1016/j.bbrc.2017.12.129. Epub 2017 Dec 24.

DNA methylation signal has a major role in the response of human breast cancer cells to the microenvironment. Mathot P, Grandin M, Devailly G, Souaze F, Cahais V, Moran S, Campone M, Herceg Z, Esteller M, Juin P, Mehlen P, Dante R. Oncogenesis. 2017 Oct 23;6(10):e390. doi: 10.1038/oncsis.2017.88.

Alu RNA accumulation induces epithelial-to-mesenchymal transition by modulating miR-566 and is associated with cancer progression. Di Ruocco F, Basso V, Rivoire M, Mehlen P, Ambati J, De Falco S, Tarallo V.Oncogene. 2018 Feb 1;37(5):627-637. doi: 10.1038/onc.2017.369. Epub 2017 Oct 9.

p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis. Napoletano F, Gibert B, Yacobi-Sharon K, Vincent S, Favrot C, Mehlen P, Girard V, Teil M, Chatelain G, Walter L, Arama E, Mollereau B. PLoS Genet. 2017 Sep 25;13(9):e1007024. doi: 10.1371/journal.pgen.1007024. eCollection 2017 Sep.

Reciprocal antagonism between the netrin-1 receptor uncoordinated-phenotype-5A (UNC5A) and the hepatitis C virus. Plissonnier ML, Lahlali T, Raab M, Michelet M, Romero-López C, Rivoire M, Strebhardt K, Durantel D, Levrero M, Mehlen P, Zoulim F, Parent R. Oncogene. 2017 Nov 30;36(48):6712-6724. doi: 10.1038/onc.2017.271. Epub 2017 Aug 7.

Non-canonical NOTCH3 signalling limits tumour angiogenesis. Lin S, Negulescu A, Bulusu S, Gibert B, Delcros JG, Ducarouge B, Rama N, Gadot N, Treilleux I, Saintigny P, Meurette O, Mehlen P. Nat Commun. 2017 Jul 18;8:16074. doi: 10.1038/ncomms16074.

Molecular characterization of Netrin-1 and APP receptor binding: New leads to block the progression of senile plaques in Alzheimer's disease. Borel F, Marzocca F, Delcros JG, Rama N, Mehlen P, Ferrer JL. Biochem Biophys Res Commun. 2017 Jul 1;488(3):466-470. doi: 10.1016/j.bbrc.2017.05.056. Epub 2017 May 10

Floor-plate-derived netrin-1 is dispensable for commissural axon guidance. Dominici C, Moreno-Bravo JA, Puiggros SR, Rappeneau Q, Rama N, Vieugue P, Bernet A, Mehlen P, Chédotal A. Nature. 2017 May 18;545(7654):350-354. doi: 10.1038/nature22331. Epub 2017 Apr 26.

Ephrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the dependence receptor EphA4. Royet A, Broutier L, Coissieux MM, Malleval C, Gadot N, Maillet D, Gratadou-Hupon L, Bernet A, Nony P, Treilleux I, Honnorat J, Liebl D, Pelletier L, Berger F, Meyronet D, Castets M, Mehlen P. Oncotarget. 2017 Apr 4;8(14):23750-23759. doi: 10.18632/oncotarget.16077.


2016

Netrin-1 Protects Hepatocytes Against Cell Death Through Sustained Translation During the Unfolded Protein Response. Lahlali T, Plissonnier ML, Romero-López C, Michelet M, Ducarouge B, Berzal-Herranz A, Zoulim F, Mehlen P, Parent R. Cell Mol Gastroenterol Hepatol. 2016 Jan 9;2(3):281-301.e9. doi: 10.1016/j.jcmgh.2015.12.011. eCollection 2016 May.

Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes. Reuten R, Patel TR, McDougall M, Rama N, Nikodemus D, Gibert B, Delcros JG, Prein C, Meier M, Metzger S, Zhou Z, Kaltenberg J, McKee KK, Bald T, Tüting T, Zigrino P, Djonov V, Bloch W, Clausen-Schaumann H, Poschl E, Yurchenco PD, Ehrbar M, Mehlen P, Stetefeld J, Koch M. Nat Commun. 2016 Nov 30;7:13515. doi: 10.1038/ncomms13515.

[Hepatitis C, EGFR, cirrhosis and netrin-1: potential implications for HCC onset]. Plissonnier ML, Lahlali T, Mehlen P, Parent R. Med Sci (Paris). 2016 Jun-Jul;32(6-7):566-8. doi: 10.1051/medsci/20163206013. Epub 2016 Jul 12. French. No abstract available.

Inhibition of DNA methylation promotes breast tumor sensitivity to netrin-1 interference. Grandin M, Mathot P, Devailly G, Bidet Y, Ghantous A, Favrot C, Gibert B, Gadot N, Puisieux I, Herceg Z, Delcros JG, Bernet A, Mehlen P, Dante R. EMBO Mol Med. 2016 Aug 1;8(8):863-77. doi: 10.15252/emmm.201505945. Print 2016 Aug.

Netrin-1 Interrupts Amyloid-β Amplification, Increases sAβPPα in vitro and in vivo, and Improves Cognition in a Mouse Model of Alzheimer's Disease. Spilman PR, Corset V, Gorostiza O, Poksay KS, Galvan V, Zhang J, Rao R, Peters-Libeu C, Vincelette J, McGeehan A, Dvorak-Ewell M, Beyer J, Campagna J, Bankiewicz K, Mehlen P, John V, Bredesen DE. J Alzheimers Dis. 2016 Mar 8;52(1):223-42. doi: 10.3233/JAD-151046.

Epidermal Growth Factor Receptor-Dependent Mutual Amplification between Netrin-1 and the Hepatitis C Virus. Plissonnier ML, Lahlali T, Michelet M, Lebossé F, Cottarel J, Beer M, Neveu G, Durantel D, Bartosch B, Accardi R, Clément S, Paradisi A, Devouassoux-Shisheboran M, Einav S, Mehlen P, Zoulim F, Parent R. PLoS Biol. 2016 Mar 31;14(3):e1002421. doi: 10.1371/journal.pbio.1002421. eCollection 2016 Mar.

[The netrin-1 cue regulates somatic cell reprogramming to pluripotency] Mehlen P, Lavial F. Med Sci (Paris). 2016 Mar;32(3):241-4. doi: 10.1051/medsci/20163203005. Epub 2016 Mar 23. French. No abstract available.

Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas. Broutier L, Creveaux M, Vial J, Tortereau A, Delcros JG, Chazot G, McCarron MJ, Léon S, Pangault C, Gadot N, Colombe A, Boulland ML, Blachier J, Marie JC, Traverse-Glehen A, Donzé O, Chassagne-Clément C, Salles G, Tarte K, Mehlen P, Castets M. EMBO Mol Med. 2016 Feb 1;8(2):96-104. doi: 10.15252/emmm.201505480.

Structural Decoding of the Netrin-1/UNC5 Interaction and its Therapeutical Implications in Cancers. Grandin M, Meier M, Delcros JG, Nikodemus D, Reuten R, Patel TR, Goldschneider D, Orriss G, Krahn N, Boussouar A, Abes R, Dean Y, Neves D, Bernet A, Depil S, Schneiders F, Poole K, Dante R, Koch M, Mehlen P, Stetefeld J. Cancer Cell. 2016 Feb 8;29(2):173-85. doi: 10.1016/j.ccell.2016.01.001.


 2015

Dependence Receptors and Cancer: Addiction to Trophic Ligands. Gibert B, Mehlen P. Cancer Res. 2015 Dec 15;75(24):5171-5. doi: 10.1158/0008-5472.CAN-14-3652. Epub 2015 Dec 1. Review.

Unraveling the Role of Huntingtin in Breast Cancer Metastasis. Thion MS, McGuire JR, Sousa CM, Fuhrmann L, Fitamant J, Leboucher S, Vacher S, du Montcel ST, Bièche I, Bernet A, Mehlen P, Vincent-Salomon A, Humbert S. J Natl Cancer Inst. 2015 Aug 20;107(10). pii: djv208. doi: 10.1093/jnci/djv208. Print 2015 Oct.

ϒ-secretase and LARG mediate distinct RGMa activities to control appropriate layer targeting within the optic tectum. Banerjee P, Harada H, Tassew NG, Charish J, Goldschneider D, Wallace VA, Sugita S, Mehlen P, Monnier PP. Cell Death Differ. 2016 Mar;23(3):442-53. doi: 10.1038/cdd.2015.111. Epub 2015 Aug 21.

Netrin-1 regulates somatic cell reprogramming and pluripotency maintenance. Ozmadenci D, Féraud O, Markossian S, Kress E, Ducarouge B, Gibert B, Ge J, Durand I, Gadot N, Plateroti M, Bennaceur-Griscelli A, Scoazec JY, Gil J, Deng H, Bernet A, Mehlen P, Lavial F. Nat Commun. 2015 Jul 8;6:7398. doi: 10.1038/ncomms8398.

[Quinze questions importantes à se poser en oncologie en 2015]. Blay JY, Tredan O, Ray-Coquard I, Rivoire M, Mehlen P, Puisieux A, Bachelot T. Bull Cancer. 2015 Jun;102(6 Suppl 1):S22-6. doi: 10.1016/S0007-4551(15)31214-5. Review. French.

Dynamics of MBD2 deposition across methylated DNA regions during malignant transformation of human mammary epithelial cells. Devailly G, Grandin M, Perriaud L, Mathot P, Delcros JG, Bidet Y, Morel AP, Bignon JY, Puisieux A, Mehlen P, Dante R. Nucleic Acids Res. 2015 Jul 13;43(12):5838-54. doi: 10.1093/nar/gkv508. Epub 2015 May 24.

2014

Regulation by miR181 family of the dependence receptor CDON tumor suppressive activity in neuroblastoma. Gibert B, Delloye-Bourgeois C, Gattolliat CH, Meurette O, Le Guernevel S, Fombonne J, Ducarouge B, Lavial F, Bouhallier F, Creveaux M, Negulescu AM, Bénard J, Janoueix-Lerosey I, Harel-Bellan A, Delattre O, Mehlen P. J Natl Cancer Inst. 2014 Oct 13;106(11). pii: dju318. doi: 10.1093/jnci/dju318. Print 2014 Nov.

Sonic Hedgehog promotes the survival of neural crest cells by limiting apoptosis induced by the dependence receptor CDON during branchial arch development. Delloye-Bourgeois C, Rama N, Brito J, Le Douarin N, Mehlen P. Biochem Biophys Res Commun. 2014 Sep 26;452(3):655-60. doi:10.1016/j.bbrc.2014.08.134. Epub 2014 Sep 1.

Dependence receptors and colorectal cancer. Mehlen P, Tauszig-Delamasure S. Gut. 2014 Nov;63(11):1821-9. doi: 10.1136/gutjnl-2013-306704. Epub 2014 Aug 27. Review.

Patched-1 proapoptotic activity is downregulated by modification of K1413 by the E3 ubiquitin-protein ligase Itchy homolog. Chen XL, Chinchilla P, Fombonne J, Ho L, Guix C, Keen JH, Mehlen P, Riobo NA. Mol Cell Biol. 2014 Oct;34(20):3855-66. doi: 10.1128/MCB.00960-14. Epub 2014 Aug 4.

Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases. Harter PN, Zinke J, Scholz A, Tichy J, Zachskorn C, Kvasnicka HM, Goeppert B, Delloye-Bourgeois C, Hattingen E, Senft C, Steinbach JP, Plate KH, Mehlen P, Schulte D, Mittelbronn M PLoS One. 2014 Mar 19;9(3):e92311. doi: 10.1371/journal.pone.0092311. eCollection 2014.


2013

Delcros JG, Mehlen P.Dependence receptors: life or death choices. (2013) Bull Cancer. Dec;100(12):1261-74

Paradisi A, Creveaux M, Gibert B, Devailly G, Redoulez E, Neves D, Cleyssac E, Treilleux I, Klein C, Niederfellner G, Cassier PA, Bernet A, Mehlen P.  Combining chemotherapeutic agents and netrin-1 interference potentiates cancer cell death. (2013) EMBO Mol Med. Dec;5(12):1821-34.

Semaphorin 3E Suppresses Tumor Cell Death Triggered by the Plexin D1 Dependence Receptor in Metastatic Breast Cancers. Luchino J, Hocine M, Amoureux MC, Gibert B, Bernet A, Royet A, Treilleux I, Lécine P, Borg JP, Mehlen P, Chauvet S, Mann F. Cancer Cell. 2013 Nov 11;24(5):673-85

Caspase-generated fragment of the Met receptor favors apoptosis via the intrinsic pathway independently of its tyrosine kinase activity. Lefebvre J, Muharram G, Leroy C, Kherrouche Z, Montagne R, Ichim G, Tauszig-Delamasure S, Chotteau-Lelievre A, Brenner C, Mehlen P, Tulasne D. (2013) Cell Death Dis. Oct 17;4:e871

The Dependence Receptor TrkC Triggers Mitochondria-Dependent Apoptosis upon Cobra-1 Recruitment. Ichim G, Genevois AL, Ménard M, Yu LY, Coelho-Aguiar JM, Llambi F, Jarrosson-Wuilleme L, Lefebvre J, Tulasne D, Dupin E, Le Douarin N, Arumäe U, Tauszig-Delamasure S, Mehlen P. (2013) Mol Cell. Sep 12;51(5):632-46.

Sonic Hedgehog promotes tumor cell survival by inhibiting CDON pro-apoptotic activity. Delloye-Bourgeois C, Gibert B, Rama N, Delcros JG, Gadot N, Scoazec JY, Krauss R, Bernet A, Mehlen P. (2013) PLoS Biol.  Aug;11(8):e1001623.

Analysis of the dominant effects mediated by wild type or R120G mutant of αB-crystallin (HspB5) towards Hsp27 (HspB1). Simon S, Dimitrova V, Gibert B, Virot S, Mounier N, Nivon M, Kretz-Remy C, Corset V, Mehlen P, Arrigo AP. (2013) PLoS One. Aug 12; 8(8):e70545

Dependence receptor UNC5D mediates nerve growth factor depletion-induced neuroblastoma regression. Zhu Y, Li Y, Haraguchi S, Yu M, Ohira M, Ozaki T, Nakagawa A, Ushijima T, Isogai E, Koseki H, Nakamura Y, Kong C, Mehlen P, Arakawa H, Nakagawara A. (2013) J Clin Invest.  Jul 1;123(7):2935-47

Dependence receptor TrkC is a putative colon cancer tumor suppressor. Genevois AL, Ichim G, Coissieux MM, Lambert MP, Lavial F, Goldschneider D, Jarrosson-Wuilleme L, Lepinasse F, Gouysse G, Herceg Z, Scoazec JY, Tauszig-Delamasure S, Mehlen P. (2013) Proc Natl Acad Sci U S A.  Feb 19;110(8):3017-22.
 

2012

Dupre A, Paradisi A, Langonnet S, Gandini A, Mehlen P, Rivoire M. Bevacizumab impairs hepatocyte proliferation after partial hepatectomy in a rabbit model. (2012) Anticancer Res. Dec;32(12):5193-200.

Rama N, Goldschneider D, Corset V, Lambert J, Pays L, Mehlen P. Amyloid precursor protein regulates netrin-1-mediated commissural axon outgrowth. (2012) J Biol Chem. Aug 24;287(35):30014-23.

Delloye-Bourgeois C, Goldschneider D, Paradisi A, Therizols G, Belin S, Hacot S, Rosa-Calatrava M, Scoazec JY, Diaz JJ, Bernet A, Mehlen P.  Nucleolar localization of a netrin-1 isoform enhances tumor cell proliferation. (2012) Sci Signal. Aug 7;5(236):ra57.

Gibert B, Eckel B, Gonin V, Goldschneider D, Fombonne J, Deux B, Mehlen P, Arrigo AP, Clézardin P, Diaz-Latoud C. Targeting heat shock protein 27 (HspB1) interferes with bone metastasis and tumour formation in vivo. (2012) Br J Cancer. Jun 26;107(1):63-70.

Ichim G, Tauszig-Delamasure S, Mehlen P.Neurotrophins and cell death. Exp Cell Res. Jul 1;318(11):1221-8.
Broutier L, Castets M. (2012) DCC, come back of a suppressor gene in colorectal cancer (2012) Med Sci (Paris). May;28(5):465-8. 

Lambert E, Coissieux MM, Laudet V, Mehlen P. Netrin-4 acts as a pro-angiogenic factor during zebrafish development. (2012) J Biol Chem. Feb 3;287(6):3987-99.

2011
DCC constrains tumour progression via its dependence receptor activity. Castets M, Broutier L, Molin Y, Brevet M, Chazot G, Gadot N, Paquet A, Mazelin L, Jarrosson-Wuilleme L, Scoazec JY, Bernet A, Mehlen P. (2011) Nature. Dec 11;482(7386):534-7.

Variants in the netrin-1 receptor UNC5C prevent apoptosis and increase risk of familial colorectal cancer. Coissieux MM, Tomsic J, Castets M, Hampel H, Tuupanen S, Andrieu N, Comeras I, Drouet Y, Lasset C, Liyanarachchi S, Mazelin L, Puisieux A, Saurin JC, Scoazec JY, Wang Q, Aaltonen L, Tanner SM, de la Chapelle A, Bernet A, Mehlen P. (2011) Gastroenterology. Dec;141(6):2039-46.

Rajasundari A, Pays L, Mehlen P, Ramesh G.  Netrin-1 overexpression in kidney proximal tubular epithelium ameliorates cisplatin nephrotoxicity. (2011) Lab Invest. Dec;91(12):1717-26.

Cabrera JR, Bouzas-Rodriguez J, Tauszig-Delamasure S, Mehlen P.  RET modulates cell adhesion via its cleavage by caspase in sympathetic neurons. (2011) J Biol Chem. Apr 22;286(16):14628-38.

Mehlen P, Delloye-Bourgeois C, Chédotal A.  Novel roles for Slits and netrins: axon guidance cues as anticancer targets? (2011) Nat Rev Cancer. Mar;11(3):188-97.

Mehlen P, Bredesen DE.  Dependence receptors: from basic research to drug development. (2011) Sci Signal. Jan 25;4(157):mr2.

2010

Mehlen P. Dependence receptors: the trophic theory revisited. (2010) Sci Signal. Dec 7;3(151):pe47.

Guenebeaud C, Goldschneider D, Castets M, Guix C, Chazot G, Delloye-Bourgeois C, Eisenberg-Lerner A, Shohat G, Zhang M, Laudet V, Kimchi A, Bernet A, Mehlen P. The dependence receptor UNC5H2/B triggers apoptosis via PP2A-mediated dephosphorylation of DAP kinase. (2010) Mol Cell. Dec 22;40(6):863-76.

Thibert C, Fombonne J. Dependence receptors: mechanisms of an announced death. (2010) Cell Cycle. Jun 1;9(11):2085-91

Goldschneider D, Mehlen P. (2010) Dependence receptors: a new paradigm in cell signaling and cancer therapy. Oncogene. Apr 1;29(13):1865-82.

Paradisi A, Mehlen P. Netrin-1, a missing link between chronic inflammation and tumor progression. (2010)Cell Cycle. Apr 1;9(7):1253-62.

Castets M, Mehlen P. Netrin-1 role in angiogenesis: to be or not to be a pro-angiogenic factor? (2010) Cell Cycle. Apr 15;9(8):1466-71.

Bouzas-Rodriguez J, Cabrera JR, Delloye-Bourgeois C, Ichim G, Delcros JG, Raquin MA, Rousseau R, Combaret V, Bénard J, Tauszig-Delamasure S, Mehlen P. Neurotrophin-3 production promotes human neuroblastoma cell survival by inhibiting TrkC-induced apoptosis. (2010) J Clin Invest. Mar;120(3):850-8.

2009

Paradisi A, Maisse C, Coissieux MM, Gadot N, Lépinasse F, Delloye-Bourgeois C, Delcros JG, Svrcek M, Neufert C, Fléjou JF, Scoazec JY & P. Mehlen. Netrin-1 up-regulation in inflammatory bowel diseases is required for colorectal cancer progression. (2009) Proc. Natl. Acad. Sci. USA Oct. 6; 106, 17146-51.

Mille F, Thibert C, Fombonne J, Rama N, Guix C, Hayashi H, Corset V, Reed JC & P. Mehlen. The Patched dependence receptor triggers apoptosis through a DRAL-caspase-9 complex. (2009). Nature Cell Biology.Jun; 11 (6), 739-46.

Lourenço FC, Galvan V, Fombonne J, Corset V, Llambi F, Müller U, Bredesen DE, Mehlen P. Netrin-1 interacts with amyloid precursor protein and regulates amyloid-beta production. (2009) Cell Death Differ.May;16(5):655-63

Delloye-Bourgeois C, Fitamant J, Paradisi A, Cappellen D, Douc-Rasy S, Raquin M.A, Stupack D, Nakagawara A, Combaret V, Puisieux A, Couanet-Valteau D, Bénard J, Bernet A & Mehlen P. Netrin-1 acts as a survival factor for aggressive neuroblastoma. (2009b) J. Exp. Medicine Apr 13; 206, 833-847.

Castets M, Coissieux MM, Delloye-Bourgeois C, Bernard L, Delcros JG, Bernet A, Laudet V & P. Mehlen.Inhibition of endothelial cell apoptosis by netrin-1 during angiogenesis.  (2009). Dev. Cell. Apr; 16, 614-620.

Fombonne J, Rabizadeh S, Banwait S, Mehlen P, Bredesen DE. Selective vulnerability in Alzheimer's disease: amyloid precursor protein and p75(NTR) interaction. (2009) Ann Neurol. Mar;65(3):294-303


2008
Fitamant J, Guenebeaud C, Coissieux MM, Guix C, Treilleux I, Scoazec JY, Bachelot T, Bernet A, Mehlen P. Netrin-1 expression confers a selective advantage for tumor cell survival in metastatic breast cancer (2008).Proc Natl Acad Sci U S A. Mar 25;105(12):4850-5. 

Paradisi A.*, Maisse C.*, Bernet A., Coissieux MM., Maccarrone M., Scoazec JY., Mehlen P. (*equaly contributed). NF-κB regulates netrin-1 expression and affects the conditional tumor suppressive activity of the netrin-1 receptors (2008). Gastroenterology 2008 135(4):1248-57 

Bernet A, Fitamant J. Netrin-1 and its receptors in tumour growth promotion (2008). Expert Opin Ther Targets. Aug;12(8):995-1007. 

2004-2007
Bernet A, Mazelin L, Coissieux MM, Gadot N, Ackerman SL, Scoazec JY, Mehlen P. Inactivation of the UNC5C Netrin-1 receptor is associated with tumor progression in colorectal malignancies (2007).Gastroenterology. Dec;133(6):1840-8. Aug 2 

Bernet A and Mehlen P. Dependence receptors: when apoptosis controls tumor progression (2007). Bull Cancer. Apr 1;94(4):E12-7. 

Mehlen P and Bernet A. Netrin Pipes up (2005). Nature Cell Biology, 7 (11),1052-3 

Bernet A and Mehlen P. Netrin-1 and its dependence receptors : function in colorectal tumorigenesis. (2005)Pathol.Biol. 53 (6). 328-333. 

Mazelin L, Bernet A, Bidaud-Bonod C, Pays L, Gespach C, Bredesen DE, Scoazec JY and Mehlen P. Netrin-1 controls colorectal tumorigenesis by regulating apoptosis (2004). Nature Sep 2 ; 431(7004), 80-84

 

Principaux financements
INSERM
CNRS
Université Claude Bernard Lyon I
Institut National du Cancer (INCa)
Association pour la Recherche sur le Cancer (ARC)
Ligue Nationale contre le Cancer (Comités de l’Ain, de l’Ardèche, de la Drôme, du Puy de Dôme, du Rhône, de Savoie et de Saône et Loire)
Agence Nationale pour la Recherche (ANR)
Région Auvergne Rhône-Alpes
Lyon Biopole
Laboratoire d'Excellence (LabEx) DevWeCan (Grand Emprunt)
Fondation pour la Recherche Médicale (FRM) 

Principales collaborations nationales
Institut Gustave Roussy (Villejuif) / Laurence ZITVOGEL
INSERM U851 (Lyon) / Jacqueline MARVEL et Thierry WALZER
Institut de Recherche Thérapeutique IRT UN Unité INSERM 892, Centre de Recherche en Cancérologie Nantes-Angers (Nantes) / Henri VIE
Institut Curie (Paris) / Sebastian AMIGORENA, Vassili SOUMELIS, …
Université Pierre et Marie Curie (Paris) / Benoit SALOMON et Gilles MARODON
INSERM U631 (CIML, Marseille) / Marc DALOD et Bernard MALISSEN
Laboratoire d'Immunologie des Tumeurs, Centre de Recherche en Cancérologie de Marseille (Marseille) / Daniel OLIVE
INRA (Jouy en Josas) / Nicolas BERTHO et Isabelle SWARTZ-CORNIL
Institut de Biologie Structurale (Grenoble) / Franck FIESCHI
Institut de Génétique Moléculaire de Montpellier (Montpellier) / Marc PIECHAZYCK
Société BASF (Lyon) / Valérie ANDRE et Nicolas BECHETOILLE
Groupe Hospitalier Pitié Salpêtrière (Paris) / Dr Jean-Baptiste BACHET
Groupe Hospitalier Universitaire Ambroise Paré (Paris) / Pr Jean-François EMILE
Hôpital de la TIMONE / Dr Sébastien SALAS
Institut Bergonié (Bordeaux) / Pr Jean Michel COINDRE, Dr Isabelle HOSTIEN, Dr Frederic CHIBON
ImmunID Technologies (Grenoble) / N. PASQUAL
Université d’Auvergne/CHU (Clermont Ferrand) / Marc BERGER
INSERM U1035 (Bordeaux) / Jean-Max PASQUET
CNRS 8619-IBBMC (Orsay) / Michel LEPOIVRE
USR3010 – LJC CNRS (Lyon) Equipe Mechano-genetics of the cell / Françoise ARGOUL
Faculté de medicine, U895 (Nice) Cell death differentiation and cancer / Dr Patrick AUBERGER

Principales collaborations internationales
Société ROCHE (Penzberg, Allemagne) Carola RIES
Société GlaxoSmithKline (Brentford, UK/Agnes Goetschel)
Brad NELSON (Victoria British Columbia, Canada)
PHARMAMAR (Carlos GALMARINI, colmenar viejo, espagne)




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