A5030226248- Acute Myeloid Leukemia Research
- Cancer-related Molecular Pathways
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Cancer, Lipids, and Metabolism
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- Chronic Myeloid Leukemia Treatments
- Autophagy in Disease and Therapy
- Sarcoma Diagnosis and Treatment
- Retinoids in leukemia and cellular processes
- Glioma Diagnosis and Treatment
- Nanoparticle-Based Drug Delivery
- Melanoma and MAPK Pathways
- Biopolymer Synthesis and Applications
- Hematopoietic Stem Cell Transplantation
- Mitochondrial Function and Pathology
- Protein Degradation and Inhibitors
- Endoplasmic Reticulum Stress and Disease
- Immune cells in cancer
- RNA Research and Splicing
- DNA Repair Mechanisms
Institut de Recherche en Cancérologie de Montpellier
2015-2024
Université de Montpellier
2014-2024
Inserm
2015-2024
Institut Regional du Cancer de Montpellier
2014-2023
La Ligue Contre le Cancer
2016-2020
Institut National de Recherche en Santé Publique
2014
Centre National de la Recherche Scientifique
2003-2007
Centre de Recherche en Biologie cellulaire de Montpellier
2007
Seiko Holdings (Japan)
2004
University of Cologne
2001-2004
Abstract Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be enriched in quiescent immature leukemic stem (LSC). To validate this hypothesis vivo, we developed a clinically relevant chemotherapeutic approach treating patient-derived xenografts (PDX) with cytarabine (AraC). AraC residual AML neither immature, nor LSCs. Strikingly, AraC-resistant preexisting and persisting displayed high levels of reactive oxygen species, showed increased mitochondrial mass,...
The RING finger proteins HdmX and Hdm2 share significant structural functional similarity. is a member of the family ubiquitin-protein ligases E3 targets tumor suppressor protein p53 for degradation. Although also binds to p53, does not induce Moreover, has been reported interfere with degradation in overexpression experiments. To obtain insight into mechanism by which interferes degradation, we studied effect on activity vitro . Surprisingly, this revealed that stimulates Hdm2-mediated...
The E6 oncoprotein of human papillomaviruses (HPVs) that are associated with cervical cancer utilizes the cellular ubiquitin–protein ligase E6-AP to target tumor suppressor p53 for degradation. In normal cells (i.e., in absence E6), is also a ubiquitin–proteasome pathway. Under these conditions, however, degradation mediated by Mdm2 rather than E6-AP. Here we show mutational analysis that, surprisingly, structural requirements serve as proteolytic substrate differ between proteins derived...
Mutations in IDH induce epigenetic and transcriptional reprogramming, differentiation bias, susceptibility to mitochondrial inhibitors cancer cells. Here, we first show that cell lines, PDXs, patients with acute myeloid leukemia (AML) harboring an mutation displayed enhanced oxidative metabolism. Along increase TCA cycle intermediates, this AML-specific metabolic behavior mechanistically occurred through the electron transport chain complex I activity, respiration, methylation-driven...
The histone acetyl transferase Tip60 (HTATIP) shares many properties with the tumor suppressor p53 (TP53). Both proteins are involved in cellular response to DNA damage, subjected proteasomal digestion following Mdm2-mediated ubiquitination, and accumulate after UV irradiation. We found here that knock-down of affects p53-dependent actinomycin D treatment, most likely because it inhibits p21 (CDKN1A) accumulation. Moreover, is required for activate endogenous promoter, suggesting functions...
Significance Autophagy allows the lysosomal degradation of intracellular material. It is a tightly regulated process controlled by tumor-suppressor gene p53, among others. Here we report unique regulator autophagy, BAT3, which modulates localization enzyme p300, an that adds some acetyl residues on targets proteins (acetylation) to modulate their activity. To stimulate BAT3 acetylation p53 p300 in nucleus, but limits p300-dependent ATG7, protein specific for cytosol. Thus, acts both cytosol...
Acute myeloid leukemia (AML) is characterized by the accumulation of malignant blasts with impaired differentiation programs caused recurrent mutations, such as isocitrate dehydrogenase (IDH) mutations found in 15% AML patients. These result production oncometabolite (R)-2-hydroxyglutarate (2-HG), leading to a hypermethylation phenotype that dysregulates hematopoietic differentiation. In this study, we identified mutant R132H IDH1-specific gene signatures regulated key transcription factors,...
Patients with acute myeloid leukemia and a high white blood cell count are at increased risk of early death relapse. Because mediators inflammation contribute to leukostasis chemoresistance, dexamethasone added chemotherapy could improve outcomes. This retrospective study evaluated the impact adding or not in cohort 160 patients least 50×109 cells. In silico studies, primary samples, leukemic lines, xenograft mouse models were used explore antileukemic activity dexamethasone. There was no...
Background: In Acute Myeloid Leukemia (AML), a complete response to chemotherapy is usually obtained after conventional but overall patient survival poor due highly frequent relapses. As opposed chronic myeloid leukemia, B lymphoma or multiple myeloma, AML one of the rare malignant hemopathies therapy which has not significantly improved during past 30 years despite intense research efforts. One promising approach determine metabolic dependencies in cells. Moreover, two key enzymes,...
Cetuximab, a monoclonal antibody against EGFR used for the treatment of colorectal cancer (CRC), is ineffective in many patients. The aim this study was to identify signalling pathways activated by cetuximab CRC cells and define new biomarker response.We vitro, vivo models clinical samples assess role p38 FOXO3a mechanism action.We show that activates MAPK p38. Specifically, inhibition reduced efficacy on cell growth death. At molecular level, transcription factor promotes its nuclear...
Chromatin-bound MDM2 regulates serine metabolism and nucleotide synthesis to sustain tumor growth in liposarcoma.
The lysosomal protease cathepsin D (Cath-D) is overproduced in breast cancer cells (BCC) and supports tumor growth metastasis formation. Here, we describe the mechanism whereby Cath-D accumulated nucleus of ERα-positive (ER+) BCC. We identified TRPS1 (tricho-rhino-phalangeal-syndrome 1), a repressor GATA-mediated transcription, BAT3 (Scythe/BAG6), nucleo-cytoplasmic shuttling chaperone protein, as new Cath-D-interacting nuclear proteins. binds to ER+ BCC they partially co-localize at surface...
Glycolysis is essential to support cancer cell proliferation, even in the presence of oxygen. The transcriptional co-regulator RIP140 represses activity transcription factors that drive proliferation and metabolism plays a role mammary tumorigenesis. Here we use metabolic assays demonstrate RIP140-deficiency causes glycolysis-dependent increase breast tumor growth. We further reduces glucose transporter GLUT3 gene, by inhibiting hypoxia inducible factor HIF-2α cooperation with p53....
Pancreatic ductal adenocarcinoma (PDAC) remains one of the human cancers with poorest prognosis. Interestingly, we found that mitochondrial respiration in primary PDAC cells depends mainly on fatty acid oxidation (FAO) to meet basic energy requirements. Therefore, treated perhexiline, a well-recognized FAO inhibitor used cardiac diseases. Some respond efficiently which acts synergistically chemotherapy (gemcitabine) vitro and two xenografts vivo. Importantly, perhexiline combination...
Dedifferentiated liposarcoma (DDLPS) is the most frequent high-grade soft tissue sarcoma subtype. It characterized by a component of undifferentiated tumor cells coexisting with well-differentiated adipocytic cells. Both dedifferentiated (DD) and (WD) components exhibit MDM2 amplification, however their cellular origin remains elusive. Using single-cell RNA sequencing, DNA in situ multiplex immunofluorescence functional assays paired WD DD from primary DDLPS tumors, we characterize...
A growing body of evidence suggests that the multifunctional protein E4F1 is involved in signaling pathways play essential roles during normal development and tumorigenesis. We generated conditional knockout mice to address functions vivo newborn adult skin. inactivation entire skin or basal compartment epidermis induces homeostasis defects, as evidenced by transient hyperplasia interfollicular epithelium alteration keratinocyte differentiation, followed loss cellularity severe ulcerations....