A5015748000- Fibroblast Growth Factor Research
- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Signaling Pathways in Disease
- Cellular Mechanics and Interactions
- Enzyme function and inhibition
- Cell death mechanisms and regulation
- Acute Myeloid Leukemia Research
- Microtubule and mitosis dynamics
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer Cells and Metastasis
- Mechanisms of cancer metastasis
- Protein Degradation and Inhibitors
- Synthesis and Characterization of Heterocyclic Compounds
- Ocular Oncology and Treatments
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Mast cells and histamine
- Multiple Myeloma Research and Treatments
- Phagocytosis and Immune Regulation
- Pancreatic and Hepatic Oncology Research
- 3D Printing in Biomedical Research
- Cancer-related Molecular Pathways
- Retinoids in leukemia and cellular processes
Institut des Hautes Études Scientifiques
2018-2021
Servier (France)
2018-2021
Plateforme Technologique d'Innovation Biomédicale
2020
AVL (France)
2018-2019
Université Paris Sciences et Lettres
2016-2018
Institut Curie
2008-2018
Centre National de la Recherche Scientifique
2008-2017
Novartis (France)
2016
Novartis Institutes for BioMedical Research
2016
Novartis (United States)
2016
Invasive cancer cells are believed to breach the basement membrane (BM) using specialized protrusions called invadopodia. We found that crossing of a native BM is three-stage process: invadopodia indeed form and perforate BM, elongate into mature invadopodia, then guide cell toward stromal compartment. studied remodeling cytoskeleton networks during formation elongation ultrastructural analysis, spatial distribution molecular markers, RNA interference silencing protein expression. show...
At the stage of carcinoma in situ, basement membrane (BM) segregates tumor cells from stroma. This barrier must be breached to allow dissemination adjacent tissues. Cancer can perforate BM using proteolysis; however, whether stromal play a role this process remains unknown. Here we show that an abundant cell population, cancer-associated fibroblasts (CAFs), promote cancer invasion through BM. CAFs facilitate breaching matrix metalloproteinase-independent manner. Instead, pull, stretch, and...
Abstract Cancer cells become metastatic by acquiring a motile and invasive phenotype. This step requires remodeling of the actin cytoskeleton expression exploratory, sensory organelles known as filopodia. Aberrant β-catenin-TCF target gene activation plays major role in colorectal cancer development. We identified fascin1, key component filopodia, signaling cells. Fascin1 mRNA protein were increased primary cancers stage-dependent manner. was exclusively localized at front tumors also...
Abstract Non-small cell lung cancer (NSCLC) tumors harboring mutations in EGFR ultimately relapse to therapy with tyrosine kinase inhibitors (EGFR TKIs). Here, we show that resistant cells without the p.T790M or other acquired are sensitive Aurora B (AURKB) barasertib and S49076. Phospho-histone H3 (pH3), a major product of AURKB, is increased most treatment AURKB reduces levels pH3, triggering G1/S arrest polyploidy. Senescence subsequently induced while, their absence, polyploidy followed...
The TMPRSS2:ERG gene fusion is common in androgen receptor (AR) positive prostate cancers, yet its function remains poorly understood. From a screen for functionally relevant ERG interactors, we identify the arginine methyltransferase PRMT5. recruits PRMT5 to AR-target genes, where methylates AR on 761. This attenuates recruitment and transcription of genes expressed differentiated epithelium. AR-inhibitory restricted TMPRSS2:ERG-positive cancer cells. Mutation this methylation site results...
Preclinical evaluation of the simultaneous inhibition MCL-1 and BCL-2 with combination S63845 venetoclax in multiple myelomaApoptotic evasion has been postulated as one main mechanisms myeloma (MM) cell survival. 1,2The intrinsic apoptotic pathway, tightly regulated by protein family, is initiated intracellularly sensed stress signals ultimately leads to permeabilization outer mitochondrial membrane.Tumor cells can keep this pathway inactivated, part, through overexpression BCL-2, BCL-XL or...
Uveal melanoma (UM) is the most frequent malignant ocular tumor in adults. While primary efficiently treated by surgery and/or radiotherapy, about one third of UM patients develop metastases, for which no effective treatment currently available. The PKC, MAPK and PI3K/AKT/mTOR signaling cascades have been shown to be associated with growth. However, none compounds against those pathways results regression when used as single agents. To identify more therapeutic strategies patients, we...
Abstract Improving survival outcomes in adult B-cell acute lymphoblastic leukemia (B-ALL) remains a clinical challenge. Relapsed disease has poor prognosis despite the use of tyrosine kinase inhibitors (TKIs) for Philadelphia chromosome positive (Ph+ ALL) cases and immunotherapeutic approaches, including blinatumomab chimeric antigen receptor T cells. Targeting aberrant cell pathways with selective small molecule BH3-mimetic BCL-2 (venetoclax, S55746), BCL-XL (A1331852), or MCL1 (S63845) is...
Tankyrases (TNKS) play roles in Wnt signaling, telomere homeostasis, and mitosis, offering attractive targets for anticancer treatment. Using unbiased combination screening a large panel of cancer cell lines, we have identified strong synergy between TNKS MEK inhibitors (MEKi) KRAS-mutant cells. Our study uncovers novel function the relief feedback loop induced by inhibition on FGFR2 signaling pathway. Moreover, dual leads to more robust apoptosis antitumor activity both vitro vivo than...
Triple-negative breast cancer (TNBC) is an aggressive form of with high risk relapse and metastasis. TNBC a heterogeneous disease comprising different molecular subtypes including those mesenchymal features. The tyrosine kinase AXL expressed in cells plays role drug resistance, migration We confirm that more compared to luminal cells, its invalidation impairs cell while having no or little effect on viability. Here, we found controls directed migration. observed displays polarized...
Abstract One of the hallmarks cancer is evasion apoptosis. The B-cell lymphoma-2 (Bcl-2) family proteins represents a crucial point control Bcl-2 comprises both pro- and anti-apoptotic members, latter which (Bcl-2, Bcl-xL, Bcl-w, Mcl-1 Bcl-2A1) are often overexpressed in cells, supporting their aberrant survival. Thus, these have become an attractive target for therapy. BH3 mimetics been shown to bind binding groove members inhibit function, resulting apoptotic cell death, one such mimetic,...
Abstract The B-cell Lymphoma 2 (BCL-2) gene family encodes pro-apoptotic and anti-apoptotic proteins that are key regulators of the apoptotic process. Overexpression pro-survival member BCL-2 is a well-established mechanism contributing to oncogenesis chemoresistance in several cancers, including lymphoma leukemia. Venetoclax (Venclexta™), selective inhibitor, first new class anti-cancer drugs, called BH3 mimetics, be approved for CLL AML. Here, we describe identification novel potent...