A5031663089- Pancreatic and Hepatic Oncology Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer Genomics and Diagnostics
- Angiogenesis and VEGF in Cancer
- Neuroendocrine Tumor Research Advances
- Pancreatic function and diabetes
- Ferroptosis and cancer prognosis
- Cellular Mechanics and Interactions
- Cancer Cells and Metastasis
- Pancreatitis Pathology and Treatment
- Lymphatic System and Diseases
- 3D Printing in Biomedical Research
- Chronic Lymphocytic Leukemia Research
- Autophagy in Disease and Therapy
- Phagocytosis and Immune Regulation
- Cancer, Hypoxia, and Metabolism
- Ovarian cancer diagnosis and treatment
- Circular RNAs in diseases
- Renal cell carcinoma treatment
- Cancer-related Molecular Pathways
- Galectins and Cancer Biology
- Biomarkers in Disease Mechanisms
- Biochemical and Molecular Research
- Protein Kinase Regulation and GTPase Signaling
- Lung Cancer Research Studies
Inserm
2016-2025
Centre National de la Recherche Scientifique
2009-2025
Centre de Recherche en Cancérologie de Toulouse
2016-2025
Université Toulouse III - Paul Sabatier
2016-2025
Laboratoire d'Analyse et d'Architecture des Systèmes
2025
Université de Toulouse
2014-2025
Laboratoire Hubert Curien
2025
Toxalim Research Centre in Food Toxicology
2025
École Nationale Vétérinaire de Toulouse
2025
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2025
The p110 isoforms of phosphoinositide 3-kinase (PI3K) are acutely regulated by extracellular stimuli. class IA PI3K catalytic subunits (p110alpha, p110beta, and p110delta) occur in complex with a Src homology 2 (SH2) domain-containing p85 regulatory subunit, which has been shown to link p110alpha p110delta Tyr kinase signaling pathways. p84/p101 the p110gamma IB lack SH2 domains instead couple G protein-coupled receptors (GPCRs). Here, we show, using small-molecule inhibitors selectivity for...
Mechanical stresses, including compression, arise during cancer progression. In solid cancer, especially breast and pancreatic cancers, the rapid tumor growth environment remodeling explain their high intensity of compressive forces. However, sensitivity compressed cells to targeted therapies remains poorly known. cells, pharmacological PI3K inactivation decreased cell number induced apoptosis. These effects were accentuated when we applied 2D compression forces in mechanically responsive...
PI3K signaling is thought to mediate leptin and insulin action in hypothalamic pro-opiomelanocortin (POMC) agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, through largely unknown mechanisms. We inactivated either p110α or p110β catalytic subunits these neurons demonstrate a dominant role for the latter homeostasis regulation. In POMC inactivation prevented insulin- leptin-stimulated electrophysiological responses. POMCp110β null mice exhibited central resistance,...
Abstract Defeating pancreatic cancer resistance to the chemotherapeutic drug gemcitabine remains a challenge treat this deadly cancer. Targeting sphingolipid metabolism for improving tumor chemosensitivity has recently emerged as promising strategy. The fine balance between intracellular levels of prosurvival sphingosine-1-phosphate (S1P) and proapoptotic ceramide sphingolipids determines cell fate. Among enzymes that control metabolism, sphingosine kinase-1 (SphK1), tumor-associated protein...
Increased PI 3-kinase (PI3K) signaling in pancreatic ductal adenocarcinoma (PDAC) correlates with poor prognosis, but the role of class I PI3K isoforms during its induction remains unclear. Using genetically engineered mice and pharmacological isoform-selective inhibitors, we found that p110α isoform is a major enzyme for PDAC development induced by combination genetic nongenetic factors. Inactivation this single blocked irreversible transition exocrine acinar cells into preneoplastic...
Various tumors metastasize via lymph vessels and nodes to distant organs. Even though are hypoxic, the mechanisms of how hypoxia regulates lymphangiogenesis remain poorly characterized. Here, we show that reduced vascular endothelial growth factor C (VEGF-C) transcription cap-dependent translation upregulation hypophosphorylated 4E-binding protein 1 (4E-BP1). However, initiation VEGF-C was induced by through an internal ribosome entry site (IRES)-dependent mechanism. IRES-dependent...
Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of pancreas. It has shown a poor prognosis and rising incidence in developed world. Other pathologies associated with this tissue include pancreatitis, risk condition for pancreatic cancer. The onset both pancreatitis cancer follows pattern: exocrine acinar cells undergo transdifferentiation to duct that triggers 3D restructuration tissue. However, exact mechanism underlying process remains partially undefined. Further...
While many cellular mechanisms leading to chemotherapeutic resistance have been identified, there is an increasing realization that tumor-stroma interactions also play important role. In particular, mechanical alterations are inherent solid cancer progression and profoundly impact cell physiology. Here, we explore the influence of compressive stress on efficacy chemotherapeutics in pancreatic spheroids. We find increased leads decreased drug efficacy. Theoretical modeling experiments suggest...
Somatostatin receptor subtype 2 (sst2) gene expression is lost in 90% of human pancreatic adenocarcinomas. We previously demonstrated that stable sst2 transfection BxPC-3 cells, which do not endogenously express sst2, inhibits cell proliferation, tumorigenicity, and metastasis. These effects occur as a consequence an autocrine sst2-dependent loop, whereby induces its own ligand, somatostatin. Here we investigated whether apoptosis sst2-transfected cells. Expression induced 4.4- ± 0.05-fold...
Understanding the direct, tumor cell–intrinsic effects of PI 3-kinase (PI3K) has been a key focus research to date. Here, we report that cancer cell–extrinsic PI3K activity, mediated by p110α isoform PI3K, contributes in an unexpected way angiogenesis. In syngeneic mouse models, inactivation stromal led increased vascular density, reduced vessel size, and altered pericyte coverage. This vascularity lacked functionality, correlating with enhanced hypoxia necrosis, growth. The role...
The PI3K (phosphoinositide 3-kinase) pathway is commonly activated in cancer as a consequence of inactivation the tumour suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10), major negative regulator signalling. In line with this important role PTEN, mice that are heterozygous for PTEN-null allele (PTEN+/− mice) spontaneously develop variety tumours multiple organs. phosphatase selectivity PtdIns(3,4,5)P3, which produced by class I isoforms (p110α, p110β, p110γ p110δ)....
Transforming growth factor beta (TGFβ) acts either as a tumor suppressor or an oncogene, depending on the cellular context and time of activation. TGFβ activates canonical SMAD pathway through its interaction with serine/threonine kinase type I II heterotetrameric receptors. Previous studies investigating TGFβ-mediated signaling in pancreas relied loss-of-function approaches ligand overexpression, effects acinar cells have so far remained elusive.
Objective— Estrogens exert beneficial effect on the blood vascular system. However, their role lymphatic system has been poorly investigated. We studied protective of 17β estradiol—the most potent endogenous estrogen—in lymphedema—a dysfunction, which results in a massive fluid and fat accumulation limb. Approach Results— Screening DNA motifs able to mobilize ERs (estrogen receptors) quantitative real-time polymerase chain reaction analysis revealed that estradiol promotes transcriptional...
Abstract Cytotoxic therapy for breast cancer inhibits the growth of primary tumors, but promotes metastasis to sentinel lymph nodes through lymphatic system. However, effect first-line chemotherapy on endothelium has been poorly investigated. In this study, we determined that paclitaxel, anti-cancer drug approved treatment metastatic or locally advanced cancer, induces endothelial cell (LEC) autophagy increase metastases. While paclitaxel was largely efficacious in inhibiting LEC adhesion,...