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BDNF and Netrin-1 repression by C/EBPβ in the gut triggers Parkinson's disease pathologies, associated with constipation and motor dysfunctions.

Eun Hee Ahn, Seong Su Kang, Xia Liu, Xuebing Cao, Soo Young Choi, Laura Musazzi, Patrick Mehlen, Keqiang Ye,

Chronic constipation is one of the most prominent prodromal symptoms in Parkinson's disease (PD), and Lewy bodies, enriched with aggregated α-Synuclein (α-Syn), propagation from the gut into the brain has been proposed to play a key role in PD etiopathogenesis. BDNF (Brain-derived neurotrophic factor) and Netrin-1 promote both neuronal survival ... Read more >>

Prog. Neurobiol. (Progress in neurobiology)
[2020, :101905]

Cited: 0 times

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Netrin-1 promotes naive pluripotency through Neo1 and Unc5b co-regulation of Wnt and MAPK signalling.

Aurélia Huyghe, Giacomo Furlan, Duygu Ozmadenci, Christina Galonska, Jocelyn Charlton, Xavier Gaume, Noémie Combémorel, Christina Riemenschneider, Nicolas Allègre, Jenny Zhang, Pauline Wajda, Nicolas Rama, Pauline Vieugué, Isabelle Durand, Marie Brevet, Nicolas Gadot, Thomas Imhof, Bradley J Merrill, Manuel Koch, Patrick Mehlen, Claire Chazaud, Alexander Meissner, Fabrice Lavial,

In mouse embryonic stem cells (mESCs), chemical blockade of Gsk3α/β and Mek1/2 (2i) instructs a self-renewing ground state whose endogenous inducers are unknown. Here we show that the axon guidance cue Netrin-1 promotes naive pluripotency by triggering profound signalling, transcriptomic and epigenetic changes in mESCs. Furthermore, we demonstrate that Netrin-1 ... Read more >>

Nat. Cell Biol. (Nature cell biology)
[2020, 22(4):389-400]

Cited: 0 times

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Neogenin neutralization prevents photoreceptor loss in inherited retinal degeneration.

Jason Charish, Alireza P Shabanzadeh, Danian Chen, Patrick Mehlen, Santhosh Sethuramanujam, Hidekiyo Harada, Vera L Bonilha, Gautam Awatramani, Rod Bremner, Philippe P Monnier,

Inherited retinal degenerations (IRDs) are characterized by the progressive loss of photoreceptors and represent one of the most prevalent causes of blindness among working-age populations. Cyclic nucleotide dysregulation is a common pathological feature linked to numerous forms of IRD, yet the precise mechanisms through which this contributes to photoreceptor death ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2020, 130(4):2054-2068]

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Blocking SHH/Patched Interaction Triggers Tumor Growth Inhibition through Patched-Induced Apoptosis.

Pierre-Antoine Bissey, Pauline Mathot, Catherine Guix, Mélissa Jasmin, Isabelle Goddard, Clélia Costechareyre, Nicolas Gadot, Jean-Guy Delcros, Sachitanand M Mali, Rudi Fasan, André-Patrick Arrigo, Robert Dante, Gabriel Ichim, Patrick Mehlen, Joanna Fombonne,

The Sonic Hedgehog (SHH) pathway plays a key role in cancer. Alterations of SHH canonical signaling, causally linked to tumor progression, have become rational targets for cancer therapy. However, Smoothened (SMO) inhibitors have failed to show clinical benefit in patients with cancers displaying SHH autocrine/paracrine expression. We reported earlier that ... Read more >>

Cancer Res. (Cancer research)
[2020, 80(10):1970-1980]

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Actualités en recherche en oncologie : l’essentiel du 4e Symposium International 2019 du Centre de Recherche en Cancérologie de Lyon.

Frédéric Catez, Nicole Dalla-Venezia, Jean-Jacques Diaz, Bertrand Dubois, Anthony Ferrari, Boris Guyot, Virginie Marcel, Maria Ouzounova, Roxane M Pommier, Alain Viari, Patrick Mehlen,

Bull Cancer (Bulletin du cancer)
[2020, 107(1):136-140]

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Netrin-1 and Its Receptor DCC Are Causally Implicated in Melanoma Progression.

Amina Boussouar, Antonin Tortereau, Ambroise Manceau, Andrea Paradisi, Nicolas Gadot, Jonathan Vial, David Neves, Lionel Larue, Maxime Battistella, Christophe Leboeuf, Celeste Lebbé, Anne Janin, Patrick Mehlen,

Deleted in colorectal cancer (DCC), the receptor for the multifunctional cue netrin-1, acts as a tumor suppressor in intestinal cancer and lung metastasis by triggering cancer cell death when netrin-1 is lowly expressed. Recent genomic data highlighted that DCC is the third most frequently mutated gene in melanoma; we therefore ... Read more >>

Cancer Res. (Cancer research)
[2020, 80(4):747-756]

Cited: 0 times

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Cancer-Associated Fibroblasts Produce Netrin-1 to Control Cancer Cell Plasticity.

Pei-Ju Sung, Nicolas Rama, Jeromine Imbach, Stephany Fiore, Benjamin Ducarouge, David Neves, Huei-Wen Chen, David Bernard, Pan-Chyr Yang, Agnès Bernet, Stephane Depil, Patrick Mehlen,

Netrin-1 is upregulated in a large fraction of human neoplasms. In multiple animal models, interference with netrin-1 is associated with inhibition of tumor growth and metastasis. Although netrin-1 upregulation was initially described in cancer cells, we report here that in the human colorectal cancer database, the expression of netrin-1 and ... Read more >>

Cancer Res. (Cancer research)
[2019, 79(14):3651-3661]

Cited: 1 time

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Synergistic Activity of Floor-Plate- and Ventricular-Zone-Derived Netrin-1 in Spinal Cord Commissural Axon Guidance.

Juan Antonio Moreno-Bravo, Sergi Roig Puiggros, Patrick Mehlen, Alain Chédotal,

In vertebrates, commissural axons extend ventrally toward the floor plate in the spinal cord and hindbrain. Netrin-1, secreted by floor plate cells, was proposed to attract commissural axons at a distance. However, recent genetic studies in mice have shown that netrin-1 is also produced by ventricular zone (VZ) progenitors and ... Read more >>

Neuron (Neuron)
[2019, 101(4):625-634.e3]

Cited: 6 times

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The dependence receptor TrkC regulates the number of sensory neurons during DRG development.

Marie Ménard, Clélia Costechareyre, Juliana M Coelho-Aguiar, Loraine Jarrosson-Wuilleme, Nicolas Rama, Jonathan Blachier, Karine Kindbeiter, Muriel Bozon, Jorge R Cabrera, Elisabeth Dupin, Nicole Le Douarin, Patrick Mehlen, Servane Tauszig-Delamasure,

The development of the sensory nervous system is the result of fine-tuned waves of neurogenesis and apoptosis which control the appropriate number of precursors and newly generated neurons and orient them toward a specific lineage. Neurotrophins and their tyrosine-kinase receptors (RTK) orchestrate this process. They have long been in the ... Read more >>

Dev. Biol. (Developmental biology)
[2018, 442(2):249-261]

Cited: 1 time

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Notch Signaling in the Tumor Microenvironment.

Olivier Meurette, Patrick Mehlen,

The Notch signaling pathway regulates many aspects of cancer biology. Most attention has been given to its role in the transformed cell. However, it is now clear that cancer progression and metastasis depend on the bidirectional interactions between cancer cells and their environment, forming the tumor microenvironment (TME). These interactions ... Read more >>

Cancer Cell (Cancer cell)
[2018, 34(4):536-548]

Cited: 29 times

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Ultrasound molecular imaging as a non-invasive companion diagnostic for netrin-1 interference therapy in breast cancer.

Jennifer Wischhusen, Katheryne E Wilson, Jean-Guy Delcros, Rodolfo Molina-Peña, Benjamin Gibert, Shan Jiang, Jacqueline Ngo, David Goldschneider, Patrick Mehlen, Juergen K Willmann, Frederic Padilla,

In ultrasound molecular imaging (USMI), ligand-functionalized microbubbles (MBs) are used to visualize vascular endothelial targets. Netrin-1 is upregulated in 60% of metastatic breast cancers and promotes tumor progression. A novel netrin-1 interference therapy requires the assessment of netrin-1 expression prior to treatment. In this study, we studied netrin-1 as a ... Read more >>

Theranostics (Theranostics)
[2018, 8(18):5126-5142]

Cited: 1 time

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The Proto-oncogene c-Kit Inhibits Tumor Growth by Behaving as a Dependence Receptor.

Hong Wang, Amina Boussouar, Laetitia Mazelin, Servane Tauszig-Delamasure, Yan Sun, David Goldschneider, Andrea Paradisi, Patrick Mehlen,

c-Kit is a classic proto-oncogene either mutated or upregulated in cancer cells, and this leads to its constitutive kinase activation and, thus, to uncontrolled proliferation. Although the pro-oncogenic role of c-Kit is of no doubt, some observations do not fit well with c-Kit solely as a tumor-promoting moiety. We show ... Read more >>

Mol. Cell (Molecular cell)
[2018, 72(3):413-425.e5]

Cited: 5 times

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Dependence receptors - the dark side awakens.

Ana-Maria Negulescu, Patrick Mehlen,

Transmembrane receptors are usually seen as on and off switches: when the specific ligand is bound, the receptor is on and transduces a downstream signal, whereas when the ligand is absent, the receptor is off. Over the last two decades several reports have argued for an alternative view where some ... Read more >>

FEBS J. (The FEBS journal)
[2018, 285(21):3909-3924]

Cited: 4 times

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Hey1- and p53-dependent TrkC proapoptotic activity controls neuroblastoma growth.

Marie Ménard, Clélia Costechareyre, Gabriel Ichim, Jonathan Blachier, David Neves, Loraine Jarrosson-Wuilleme, Reinhard Depping, Jan Koster, Pierre Saintigny, Patrick Mehlen, Servane Tauszig-Delamasure,

The neurotrophin-3 (NT-3) receptor tropomyosin receptor kinase C (TrkC/NTRK3) has been described as a dependence receptor and, as such, triggers apoptosis in the absence of its ligand NT-3. This proapoptotic activity has been proposed to confer a tumor suppressor activity to this classic tyrosine kinase receptor (RTK). By investigating interacting ... Read more >>

PLoS Biol. (PLoS biology)
[2018, 16(5):e2002912]

Cited: 5 times

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The Ectodysplasin receptor EDAR acts as a tumor suppressor in melanoma by conditionally inducing cell death.

Jonathan Vial, Amélie Royet, Philippe Cassier, Antonin Tortereau, Sarah Dinvaut, Denis Maillet, Lise Gratadou-Hupon, Marion Creveaux, Alexa Sadier, Garance Tondeur, Sophie Léon, Lauriane Depaepe, Sophie Pantalacci, Arnaud de la Fouchardière, Olivier Micheau, Stéphane Dalle, Vincent Laudet, Patrick Mehlen, Marie Castets,

Ectodysplasin receptor EDAR is seen as a typical Tumor Necrosis Factor receptor (TNFR) family member known to interact with its ligand Eda-A1, and signaling mainly through the nuclear factor-kappaB (NF-κB) and c-jun N-terminal kinases pathways. Mutations in genes that encode proteins involved in EDAR transduction cascade cause anhidrotic ectodermal dysplasia. ... Read more >>

Cell Death Differ. (Cell death and differentiation)
[2019, 26(3):443-454]

Cited: 1 time

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Hepatocellular carcinoma-associated depletion of the netrin-1 receptor Uncoordinated Phenotype-5A (UNC5A) skews the hepatic unfolded protein response towards prosurvival outcomes.

Romain Barnault, Thomas Lahlali, Marie-Laure Plissonnier, Cristina Romero-López, Noémie Laverdure, Benjamin Ducarouge, Michel Rivoire, Patrick Mehlen, Fabien Zoulim, Romain Parent,

In the liver, HBV and HCV infections, exposure to toxics, genetic and metabolic disorders may induce endoplasmic reticulum (ER) stress and the unfolding protein response (UPR). The UPR allows cells to reach ER homeostasis after lumen overload, but also fosters survival of damaged cells and therefore HCC onset. Dependence receptors ... Read more >>

Biochem. Biophys. Res. Commun. (Biochemical and biophysical research communications)
[2018, 495(4):2425-2431]

Cited: 1 time

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Commissural neurons transgress the CNS/PNS boundary in absence of ventricular zone-derived netrin 1.

Juan Antonio Moreno-Bravo, Sergi Roig Puiggros, Heike Blockus, Chloé Dominici, Pavol Zelina, Patrick Mehlen, Alain Chédotal,

During the development of the central nervous system (CNS), only motor axons project into peripheral nerves. Little is known about the cellular and molecular mechanisms that control the development of a boundary at the CNS surface and prevent CNS neuron emigration from the neural tube. It has previously been shown ... Read more >>

Development (Development (Cambridge, England))
[2018, 145(2):]

Cited: 2 times

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p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis.

Francesco Napoletano, Benjamin Gibert, Keren Yacobi-Sharon, Stéphane Vincent, Clémentine Favrot, Patrick Mehlen, Victor Girard, Margaux Teil, Gilles Chatelain, Ludivine Walter, Eli Arama, Bertrand Mollereau,

The importance of regulated necrosis in pathologies such as cerebral stroke and myocardial infarction is now fully recognized. However, the physiological relevance of regulated necrosis remains unclear. Here, we report a conserved role for p53 in regulating necrosis in Drosophila and mammalian spermatogenesis. We found that Drosophila p53 is required ... Read more >>

PLoS Genet. (PLoS genetics)
[2017, 13(9):e1007024]

Cited: 9 times

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Non-canonical NOTCH3 signalling limits tumour angiogenesis.

Shuheng Lin, Ana Negulescu, Sirisha Bulusu, Benjamin Gibert, Jean-Guy Delcros, Benjamin Ducarouge, Nicolas Rama, Nicolas Gadot, Isabelle Treilleux, Pierre Saintigny, Olivier Meurette, Patrick Mehlen,

Notch signalling is a causal determinant of cancer and efforts have been made to develop targeted therapies to inhibit the so-called canonical pathway. Here we describe an unexpected pro-apoptotic role of Notch3 in regulating tumour angiogenesis independently of the Notch canonical pathway. The Notch3 ligand Jagged-1 is upregulated in a ... Read more >>

Nat Commun (Nature communications)
[2017, 8:16074]

Cited: 9 times

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Ephrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the dependence receptor EphA4.

Amélie Royet, Laura Broutier, Marie-May Coissieux, Céline Malleval, Nicolas Gadot, Denis Maillet, Lise Gratadou-Hupon, Agnès Bernet, Pascale Nony, Isabelle Treilleux, Jérôme Honnorat, Daniel Liebl, Laurent Pelletier, François Berger, David Meyronet, Marie Castets, Patrick Mehlen,

EphA4, an Ephrins tyrosine kinase receptor, behaves as a dependence receptor (DR) by triggering cell apoptosis in the absence of its ligand Ephrin-B3. DRs act as conditional tumor suppressors, engaging cell death based on ligand availability; this mechanism is bypassed by overexpression of DRs ligands in some aggressive cancers. The ... Read more >>

Oncotarget (Oncotarget)
[2017, 8(14):23750-23759]

Cited: 6 times

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Molecular characterization of Netrin-1 and APP receptor binding: New leads to block the progression of senile plaques in Alzheimer's disease.

Franck Borel, Fanny Marzocca, Jean-Guy Delcros, Nicolas Rama, Patrick Mehlen, Jean-Luc Ferrer,

Alzheimer's disease is a growing concern in the context of the increasing lifespan of the populations. The work presented here is part of the fight against this threat. It supports a therapeutic approach to reduce the incidence of Alzheimer's disease, taking advantage of the specific binding of several domains of ... Read more >>

Biochem. Biophys. Res. Commun. (Biochemical and biophysical research communications)
[2017, 488(3):466-470]

Cited: 6 times

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Floor-plate-derived netrin-1 is dispensable for commissural axon guidance.

Chloé Dominici, Juan Antonio Moreno-Bravo, Sergi Roig Puiggros, Quentin Rappeneau, Nicolas Rama, Pauline Vieugue, Agnes Bernet, Patrick Mehlen, Alain Chédotal,

Netrin-1 is an evolutionarily conserved, secreted extracellular matrix protein involved in axon guidance at the central nervous system midline. Netrin-1 is expressed by cells localized at the central nervous system midline, such as those of the floor plate in vertebrate embryos. Growth cone turning assays and three-dimensional gel diffusion assays ... Read more >>

Nature (Nature)
[2017, 545(7654):350-354]

Cited: 49 times

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Inhibition of DNA methylation promotes breast tumor sensitivity to netrin-1 interference.

Mélodie Grandin, Pauline Mathot, Guillaume Devailly, Yannick Bidet, Akram Ghantous, Clementine Favrot, Benjamin Gibert, Nicolas Gadot, Isabelle Puisieux, Zdenko Herceg, Jean-Guy Delcros, Agnès Bernet, Patrick Mehlen, Robert Dante,

In a number of human cancers, NTN1 upregulation inhibits apoptosis induced by its so-called dependence receptors DCC and UNC5H, thus promoting tumor progression. In other cancers however, the selective inhibition of this dependence receptor death pathway relies on the silencing of pro-apoptotic effector proteins. We show here that a substantial ... Read more >>

EMBO Mol Med (EMBO molecular medicine)
[2016, 8(8):863-877]

Cited: 5 times

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[The netrin-1 cue regulates somatic cell reprogramming to pluripotency].

Patrick Mehlen, Fabrice Lavial,

Med Sci (Paris) (Medecine sciences : M/S)
[2016, 32(3):241-244]

Cited: 0 times

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[Hepatitis C, EGFR, cirrhosis and netrin-1: potential implications for HCC onset].

Marie-Laure Plissonnier, Thomas Lahlali, Patrick Mehlen, Romain Parent,

Med Sci (Paris) (Medecine sciences : M/S)
[2016, 32(6-7):566-568]

Cited: 0 times

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