A5074609153- Ubiquitin and proteasome pathways
- Pancreatic and Hepatic Oncology Research
- Peptidase Inhibition and Analysis
- Digestive system and related health
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Heat shock proteins research
- Endoplasmic Reticulum Stress and Disease
- Pancreatitis Pathology and Treatment
- Cellular transport and secretion
- Cell Adhesion Molecules Research
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related Molecular Pathways
- Mitochondrial Function and Pathology
- Pancreatic function and diabetes
- Epigenetics and DNA Methylation
- Glycosylation and Glycoproteins Research
- RNA Research and Splicing
- Cancer Research and Treatments
- Cancer, Lipids, and Metabolism
- Cell death mechanisms and regulation
- PARP inhibition in cancer therapy
- Cancer Cells and Metastasis
- Cellular Mechanics and Interactions
- Signaling Pathways in Disease
Centre de Recherche en Cancérologie de Marseille
2014-2024
Aix-Marseille Université
2014-2024
Inserm
2014-2024
Centre National de la Recherche Scientifique
2014-2024
Institut Pprime
2019-2022
Institut Paoli-Calmettes
2013-2022
La Ligue Contre le Cancer
2020
Cancer Research Center
2020
Université de Bordeaux
2019
Centre National pour la Recherche Scientifique et Technique (CNRST)
2019
Intrinsically disordered proteins (IDPs) are emerging as attractive drug targets by virtue of their prevalence in various diseases including cancer. Drug development targeting IDPs is challenging because they have dynamical structure features and conventional design not applicable. NUPR1 an IDP playing important role pancreatic We previously reported that Trifluoperazine (TFP), antipsychotic agent, was capable binding to inhibiting tumors growth. Unfortunately, TFP showed strong central...
Abstract Endothelial–mesenchymal transition (EndMT) is an important source of cancer-associated fibroblasts (CAFs), which facilitates tumour progression. PDAC characterised by abundant CAFs and necrosis factor-α (TNF-α). Here, we show that TNF-α strongly induces human endothelial cells to undergo EndMT. Interestingly, downregulates the expression receptor TIE1, reciprocally TIE1 overexpression partially prevents TNF-α-induced EndMT, suggesting acts, at least partially, through regulation in...
We have previously described an inverse relationship between <i>Cdx1</i> and <i>Cdx2</i> mRNA levels the extent of dysplasia severity clinical outcome in colorectal carcinoma, suggesting that altered expression these genes was associated with carcinogenesis or tumor progression. To investigate further their involvement physiopathology cancer, HT29 colon carcinoma cells show very low<i>Cdx</i> were transfected <i>Cdx1</i>and/or cDNA to elicit overexpression. Growth rate, tumorigenicity,...
The Cbl family of ubiquitin ligases in mammals contains three members, Cbl, Cbl-b, and Cbl-3, that are involved down-regulation receptor tyrosine kinases (RTKs) by mediating ubiquitination degradation. More recently, a novel pathway has been identified whereby promotes internalization EGF via CIN85/endophilin is functionally separable from the ligase activity (1Soubeyran P. Kowanetz K. Szymkiewicz I. Langdon W.Y. Dikic Nature. 2002; 416: 183-187Crossref PubMed Scopus (489) Google Scholar)....
CIN85 is a multidomain adaptor protein involved in Cbl-mediated down-regulation of epidermal growth factor (EGF) receptors. src homology 3 domains specifically bind to proline-arginine (PxxxPR) motif Cbl, and this association seems be important for EGF receptor endocytosis. Here, we report identification novel effectors, all containing one or more PxxxPR motifs, that are indispensable their mutual interactions. These effectors include phosphatidyl-inositol phosphatases SHIP-1 synaptojanin...
Abstract It was already described that genetic inhibition of NUPR1 induces tumor growth arrest. In this paper we studied the metabolism changes after downregulation in pancreatic cancer cells, which results a significant decrease OXPHOS activity with concomitant lower ATP production precedes necrotic cell death. We demonstrated mitochondrial failure loss membrane potential, strong increase ROS and relocalization mitochondria to vicinity endoplasmic reticulum (ER). addition, transcriptomic...
Establishing the interactome of cancer-associated stress protein Nuclear Protein 1 (NUPR1), we found that it binds to several hundreds proteins, including proteins involved in nuclear translocation, DNA repair, and key factors SUMO pathway. We demonstrated NUPR1 inhibitor ZZW-115, an organic synthetic molecule, competes with importins for binding NLS region NUPR1, thereby inhibiting its translocation. hypothesized, then proved, inhibition by ZZW-115 sensitizes cancer cells damage induced...
Abstract We find that NUPR1, a stress-associated intrinsically disordered protein, induced droplet formation via liquid–liquid phase separation (LLPS). NUPR1-driven LLPS was crucial for the creation of NUPR1-dependent stress granules (SGs) in pancreatic cancer cells since genetic or pharmacological inhibition by ZZW-115 NUPR1 activity impeded SGs formation. The Kras G12D mutation oncogenic stress, overexpression, and promoted development. Notably, enforced expression independently mutated ....
Intrinsically disordered proteins (IDPs) are ubiquitous in eukaryotes, and they often associated with diseases humans. The protein NUPR1 is a multifunctional IDP involved chromatin remodeling the development progression of pancreatic cancer; however, details such functions unknown. Polycomb specific transcriptional cascades gene silencing. One complex Ring finger 1 (RING1). RING1 related to aggressive tumor features multiple cancer types. In this work we characterized interaction between...
BackgroundAlthough significant advances have been made recently to characterize the biology of pancreatic ductal adenocarcinoma (PDAC), more efforts are needed improve our understanding and face challenges related aggressiveness, high mortality rate chemoresistance this disease.MethodsIn study, we perform metabolomics profiling 77 PDAC patient-derived tumor xenografts (PDTX) investigate relationship metabolic profiles with overall survival (OS) in patients, phenotypes resistance five...
The mechanisms leading to the ubiquitination and degradation of activated c-Abl kinase have not yet been identified. We found that multi-adaptor protein ArgBP2 links ubiquitin ligase Cbl. Phosphorylation Cbl by resulted in stabilization their interactions, thus facilitating Cbl-induced subsequent ArgBP2.
Abstract The poor prognosis of pancreatic cancer is due to rapid locoregional invasion, the early development metastases, and limited efficacy current therapies. To date, none identified oncogenes suppressors involved in this disease have led efficient treatments. Here, we describe that scaffold protein ArgBP2 repressed during oncogenic transformation pancreas. We could show, using a cell line model, repression participates progression disease. Interestingly, vitro analyses revealed...
We have established the phenotype of a colorectal tumor by partial sequencing 2166 transcripts that were eventually arrayed on high-density filters. These filters used for differential screening with mRNAs cancer and normal adjacent mucosa to characterize genes whose expression is altered in carcinoma. Three encoding related proteins, PAP, reg Iα Iβ, over-expressed cancer. Northern-blot analysis confirmed their was very low colonic epithelial cells, but elevated 75% tumors. Western blotting...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that shows minimal response to chemotherapy. Genetic changes involved in the progression of PDAC concern genes encode proteins related signal transduction networks. This fact reveals importance identifying role and relations between multiple signaling cascades PDAC. One major factors modulate events multidomain scaffold function by binding several simultaneously, inducing their proximity influencing outcome signaling. A...