A5070999520- TGF-β signaling in diseases
- Pancreatic and Hepatic Oncology Research
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Metabolism, Diabetes, and Cancer
- Bone Metabolism and Diseases
- Genetic factors in colorectal cancer
- NF-κB Signaling Pathways
- Cell Adhesion Molecules Research
- Wnt/β-catenin signaling in development and cancer
- Muscle Physiology and Disorders
- Peptidase Inhibition and Analysis
- Nutrition and Health in Aging
- Pancreatic function and diabetes
- Acute Myeloid Leukemia Research
- Cellular transport and secretion
- Kruppel-like factors research
- Cancer Mechanisms and Therapy
- Genetics and Neurodevelopmental Disorders
- Hippo pathway signaling and YAP/TAZ
- Fibroblast Growth Factor Research
- Biomarkers in Disease Mechanisms
- Nerve injury and regeneration
- Neurogenetic and Muscular Disorders Research
- Epigenetics and DNA Methylation
Inserm
2011-2024
Centre de Recherche Saint-Antoine
2010-2024
Sorbonne Université
2007-2024
Hôpital Saint-Antoine
1999-2022
Toxicologie, Pharmacologie et Signalisation Cellulaire
2008-2015
Génomique Fonctionnelle des Tumeurs Solides
2007
Cleveland Clinic Lerner College of Medicine
2004-2006
Cleveland Clinic
2003
Hybrigenics (France)
2001
Transforming growth factor beta (TGFbeta) induces an epithelial to mesenchymal transition (EMT) during both physiological and pathological processes; however, the mechanism underlying this is not fully elucidated. Here, we have demonstrated that TGFbeta expression of adaptor molecule disabled-2 (Dab2) concomitant with promotion EMT. We show a transient accumulation Dab2 membrane increases binding beta1 integrin. Furthermore, small interfering RNA (siRNA)-mediated silencing in mouse mammary...
Transforming growth factor-β (TGF-β) regulates a wide variety of biological processes through two types Ser/Thr transmembrane receptors: the TGF-β type I receptor and II (TβRII). Upon ligand binding, activated by TβRII propagates signals to Smad proteins, which mediate activation target genes. In this study, we identify ADAM12 (a disintegrin metalloproteinase 12) as component signaling pathway that acts association with TβRII. We found functions mechanism independent its protease activity...
CCN5 is a member of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family and was identified as an estrogen-inducible gene in estrogen receptor-positive cell lines.However, role breast carcinogenesis remains unclear.We report here that protein localized mostly cytoplasm part nucleus human tumor tissue.Using heterologous transcription assay, we demonstrate can act transcriptional repressor presumably through association with histone deacetylase 1...
The multifunctional cytokine transforming growth factor β (TGFβ)exerts many of its effects through regulation extracellular matrixcomponents, including fibronectin (FN). Although expression both TGFβand FN are essential for embryonic development and wound healing in the adult,overexpression leads to excessive deposition matrix observedin fibroproliferative disorders. We previously have demonstrated thatTGFβ-stimulated induction requires activation c-Jun N-terminalkinase (JNK) pathway;...
Smad proteins are central mediators of the transcriptional effects transforming growth factor β (TGF-β) superfamily that regulate a wide variety biological processes. Smad7, an inhibitory protein prevents TGF-β signaling by interacting with activated type I receptor, was recently shown to induce sensitization cells different forms cell death. Here we examined effect Smad7 on c-Jun N-terminal kinase (JNK) cascade and investigated role this in both apoptotic functions Smad7. The transient...
The Sma and Mad related (Smad) family proteins are critical mediators of the transforming growth factor-β (TGF-β) superfamily signaling. After TGF-β-mediated phosphorylation association with Smad4, Smad2 moves to nucleus activates expression specific genes through cooperative interactions DNA-binding proteins, including members winged-helix transcription factors, forkhead activin signal transducer (FAST)-1 FAST2. TGF-β has also been described activate other signaling pathways, such as c-Jun...
Transforming growth factor β (TGF-β) is a pleiotropic cytokine that exerts its effects through heteromeric complex of transmembrane serine/threonine kinase receptors. At least two intracellular pathways are activated by TGF-β as follows: the SAPK/JNK, involving MEKK1, MKK4, and JNK cascade, Smad pathway. Here, we report SAPK/JNK pathway inhibits Smad3 Expression dominant negative or constitutively active mutants kinases pathway, respectively, activates represses TGF-β-induced reporter...
Highlights•Enforced expression of Twist1 triggers muscle atrophy•Twist1 is de-repressed in skeletal undergoing cancer cachexia•Twist1 functions Activin/Myostatin signaling to mediate cachexia•Targeting prevents cancer-induced cachexia and prolongs survivalSummaryCancer characterized by extreme loss that results high morbidity mortality. The incidence varies among tumor types, being lowest sarcomas, whereas 90% pancreatic ductal adenocarcinoma (PDAC) patients experience severe weight loss....
Epithelial-mesenchymal transition is associated with migration, invasion, and metastasis. The translation at the tissue scale of these changes has not yet been enlightened while being essential in understanding tumor progression. Thus, biophysical tools dedicated to measurements on model systems are needed reveal impact epithelial-mesenchymal collective cell scale. Herein, using an original approach based magnetic nanoparticle insertion inside cells, we formed flattened multicellular...
Abstract Transforming growth factor-β (TGFβ) signaling is initiated by the type I, II TGFβ receptor (TβRI/TβRII) complex. Here we report formation of an alternative complex between TβRI and orphan GPR50, belonging to G protein-coupled super-family. The interaction GPR50 with induces spontaneous TβRI-dependent Smad non-Smad stabilizing active conformation competing for binding negative regulator FKBP12 TβRI. overexpression in MDA-MB-231 cells mimics anti-proliferative effect decreases tumor a...
The transcription factor Prdm16 functions as a potent suppressor of transforming growth factor-beta (TGF-β) signaling, whose inactivation is deemed essential to the progression pancreatic ductal adenocarcinoma (PDAC). Using KrasG12D-based mouse model human PDAC, we surprisingly found that ablating did not block but instead accelerated PDAC formation and progression, suggesting might function tumor in this malignancy. Subsequent genetic experiments showed along with Smad4 resulted shift from...
The phosphorylation of Smad2 and Smad3 by the transforming growth factor (TGF)-β-activated receptor kinases their subsequent heterodimerization with Smad4 translocation to nucleus form basis for a model how Smad proteins work transmit TGF-β signals. transcriptional activity Smad2-Smad4 or Smad3-Smad4 complexes can be limited corepressor Ski, which is believed interact on TGF-β-responsive promoters represses ability activate target genes assembling DNA repressor complex containing histone...
The homeodomain protein TGIF (TG-interacting factor) restricts TGF-β/Smad cytostatic signaling by interfering with the nucleocytoplasmic transit of tumor suppressor cPML. Here, we identify PHRF1 as a ubiquitin ligase that enforces decay driving its ubiquitination at lysine 130. In so doing, ensures redistribution cPML into cytoplasm, where it associates SARA and coordinates activation Smad2 TGF-β receptor. gene resides within locus 11p15.5, which displays frequent loss in wide variety...
Abstract Fibroblast growth factor-2 (FGF2) has multiple roles in cutaneous wound healing but its natural low stability prevents the development of use skin repair therapies. Here we show that FGF2 binds outer surface dermal fibroblast (DF)-derived extracellular vesicles (EVs) and this association protects from fast degradation. EVs isolated DF cultured presence harbor on their can bind purified absence cells. Remarkably, binding to is restricted a specific subpopulation EVs, which do not...
The Smad proteins are key intracellular effectors of transforming growth factor-β (TGF-β) cytokines. ability Smads to modulate transcription results from a functional cooperativity with the coactivators p300/cAMP-response element-binding protein-binding protein (CBP), or corepressors TGIF and Ski. c-Jun N-terminal kinase (JNK) pathway, another downstream target activated by TGF-β receptors, has also been suggested inhibit signaling through interaction Smad2 Smad3. Here we show that directly...
We recently showed that the antiapoptotic function of insulin requires nuclear factor κB (NF-κB) activation (Bertrand, F., Atfi, A., Cadoret, L'Allemain, G., Robin, H., Lascols, O., Capeau, J., and Cherqui, G. (1998) J. Biol. Chem.273, 2931–2938). Here we sought to identify NF-κB-dependent survival genes are activated by mediate this function. Insulin increased expression tumor necrosis receptor-associated 2 (TRAF2) mRNA protein in Chinese hamster ovary cells overexpressing receptors (IRs)....
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease that remains incurable because of late diagnosis, which renders any therapeutic intervention challenging. Most PDAC patients develop de novo diabetes, exacerbates their morbidity and mortality. How triggers diabetes still unfolding. Using mouse model Kras G12D -driven PDAC, faithfully recapitulates the progression human disease, we observed massive selective depletion β-cells, occurring very early at stages preneoplastic lesions....