Lethal AML? Calcium signalling to the rescue! - (le 30/06/2023)
Acute myeloid leukemia (AML) is characterized by genetic aberrations in hematopoietic precursors of the myeloid lineage which lead to their defective maturation/function. While intensive chemotherapy protocols result in complete remission in 50 % to 80 % of AML patients, relapse occurs in the majority of cases. While calcium signalling is a well-known contributor to cancer hallmarks, few AML related studies have focused on relevant calcium targets. Our purpose here is to highlight calcium...
- Marie-Océane Laguillaumie, Clara Lewuillon, Yasmine Touil, Loïc Lemonnier, Thierry Idziorek
Insights into the regulation of cellular Mn<sup>2+</sup> homeostasis via TMEM165 - (le 16/04/2023)
Golgi cation homeostasis is known to be crucial for many cellular processes including vesicular fusion events, protein secretion, as well as for the activity of Golgi glycosyltransferases and glycosidases. TMEM165 was identified in 2012 as the first cation transporter related to human glycosylation diseases, namely the Congenital Disorders of Glycosylation (CDG). Interestingly, divalent manganese (Mn) supplementation has been shown to suppress the observed glycosylation defects in...
- Dorothée Vicogne, Nicolas Beauval, Zoé Durin, Delphine Allorge, Kateryna Kondratska, Aurélien Haustrate, Natasha Prevarskaya, Vladimir Lupashin, Dominique Legrand, François Foulquier
Short- and Long-term Repercussions of Vancomycin on Immune Surveillance and the Efficacy of Antitumor Treatments - (le 23/03/2023)
Although antibiotic is a major contributor to shifts in the intestinal flora that may persist for up to several months after cessation, it is now increasingly recognized that its prescription may differentially influence clinical outcome of different anticancer treatments. Intense clinical and basic research efforts aim then at gaining sufficient insights about how the cooperative action between the intestinal ecosystem and immune surveillance modulates the efficacy of anticancer treatments. In...
- Thomas Paz Del Socorro, Marion Tonneau, David Pasquier, Mathias Chamaillard
Use of 2,6-diaminopurine as a potent suppressor of UGA premature stop codons in cystic fibrosis - (le 15/01/2023)
Nonsense mutations are responsible for around 10% of cases of genetic diseases, including cystic fibrosis. 2,6-diaminopurine (DAP) has recently been shown to promote efficient readthrough of UGA premature stop codons. In this study, we show that DAP can correct a nonsense mutation in the Cftr gene in vivo in a new CF mouse model, in utero, and through breastfeeding, thanks, notably, to adequate pharmacokinetic properties. DAP turns out to be very stable in plasma and is distributed throughout...
- Catherine Leroy, Sacha Spelier, Nadège Charlene Essonghe, Virginie Poix, Rebekah Kong, Patrick Gizzi, Claire Bourban, Séverine Amand, Christine Bailly, Romain Guilbert, David Hannebique, Philippe Persoons, Gwenaëlle Arhant, Anne Prévotat, Philippe Reix, Dominique Hubert, Michèle Gérardin, Mathias Chamaillard, Natalia Prevarskaya, Sylvie Rebuffat, George Shapovalov, Jeffrey Beekman, Fabrice Lejeune
Allosteric cross-talk between the hydrophobic cleft and the BH4 domain of Bcl-2 in control of inositol 1,4,5-trisphosphate receptor activity - (le 01/09/2022)
CONCLUSIONS: Bcl-2 is an important regulator of IP(3)R activity and, thus of Ca^(2+) release from internal stores and associated processes, including cellular proliferation and death. The presence of multiple regulatory domains in both proteins suggests a complex interaction. Thus, it was found that the occlusion of the hydrophobic cleft of Bcl-2 by ABT-199 disrupts IP(3)R activity, leading to Bcl-2 rebinding with smaller affinity and lesser inhibitory effect. MDs simulations of free and ABT-199...
- George Shapovalov, Abigaël Ritaine, Nadege Charlene Essonghe, Ian de Ridder, Hristina Ivanova, Spyridoula Karamanou, Anastassios Economou, Geert Bultynck, Roman Skryma, Natalia Prevarskaya
The sarcoplasmic reticulum (SR) plays an important role in calcium homeostasis. SR calcium mishandling is described in pathological conditions, such as myopathies. Here, we investigated whether the nuclear receptor subfamily 1 group D member (NR1D1, also called REV-ERBα) regulates skeletal muscle SR calcium homeostasis. Our data demonstrate that NR1D1 deficiency in mice impaired sarco/endoplasmic reticulum calcium ATPase-dependent (SERCA-dependent) SR calcium uptake. NR1D1 acts on calcium...
- Alexis Boulinguiez, Christian Duhem, Alicia Mayeuf-Louchart, Benoit Pourcet, Yasmine Sebti, Kateryna Kondratska, Valérie Montel, Stéphane Delhaye, Quentin Thorel, Justine Beauchamp, Aurore Hebras, Marion Gimenez, Marie Couvelaere, Mathilde Zecchin, Lise Ferri, Natalia Prevarskaya, Anne Forand, Christel Gentil, Jessica Ohana, France Piétri-Rouxel, Bruno Bastide, Bart Staels, Helene Duez, Steve Lancel
TRPC1 channels regulate the activation of pancreatic stellate cells through ERK1/2 and SMAD2 pathways and perpetuate their pressure-mediated activation - (le 29/07/2022)
Pancreatic stellate cell (PSC) activation is a major event occurring during pancreatic ductal adenocarcinoma (PDAC) development. Up to now mechanisms underlying their activation by mechanical cues such as the elevated tissue pressure in PDAC remain poorly understood. Here we investigate the role of one potential mechano-transducer, TRPC1 ion channel, in PSC activation. Using pre-activated human siTRPC1 and murine TRPC1-KO PSCs, we show that TRPC1 promotes αSMA (α-smooth muscle actin) expression,...
- Silviya Radoslavova, Benedikt Fels, Zoltan Pethö, Matthias Gruner, Tobias Ruck, Sven G Meuth, Antoine Folcher, Natalia Prevarskaya, Albrecht Schwab, Halima Ouadid-Ahidouch
Ca<sup>2+</sup> Signalling and Hypoxia/Acidic Tumour Microenvironment Interplay in Tumour Progression - (le 09/07/2022)
Solid tumours are characterised by an altered microenvironment (TME) from the physicochemical point of view, displaying a highly hypoxic and acidic interstitial fluid. Hypoxia results from uncontrolled proliferation, aberrant vascularization and altered cancer cell metabolism. Tumour cellular apparatus adapts to hypoxia by altering its metabolism and behaviour, increasing its migratory and metastatic abilities by the acquisition of a mesenchymal phenotype and selection of aggressive tumour cell...
- Madelaine Magalì Audero, Natalia Prevarskaya, Alessandra Fiorio Pla
Involvement of ORAI1/SOCE in Human AML Cell Lines and Primary Cells According to ABCB1 Activity, LSC Compartment and Potential Resistance to Ara-C Exposure - (le 28/05/2022)
Acute myeloid leukemia (AML) is a hematological malignancy with a high risk of relapse. This issue is associated with the development of mechanisms leading to drug resistance that are not yet fully understood. In this context, we previously showed the clinical significance of the ATP binding cassette subfamily B-member 1 (ABCB1) in AML patients, namely its association with stemness markers and an overall worth prognosis. Calcium signaling dysregulations affect numerous cellular functions and are...
- Clara Lewuillon, Aurélie Guillemette, Sofia Titah, Faruk Azam Shaik, Nathalie Jouy, Ossama Labiad, Valerio Farfariello, Marie-Océane Laguillaumie, Thierry Idziorek, Adeline Barthélémy, Pauline Peyrouze, Céline Berthon, Mehmet Cagatay Tarhan, Meyling Cheok, Bruno Quesnel, Loïc Lemonnier, Yasmine Touil
TRPM8-Rap1A Interaction Sites as Critical Determinants for Adhesion and Migration of Prostate and Other Epithelial Cancer Cells - (le 14/05/2022)
Emerging evidence indicates that the TRPM8 channel plays an important role in prostate cancer (PCa) progression, by impairing the motility of these cancer cells. Here, we reveal a novel facet of PCa motility control via direct protein-protein interaction (PPI) of the channel with the small GTPase Rap1A. The functional interaction of the two proteins was assessed by active Rap1 pull-down assays and live-cell imaging experiments. Molecular modeling analysis allowed the identification of four...
- Giorgia Chinigò, Guillaume P Grolez, Madelaine Audero, Alexandre Bokhobza, Michela Bernardini, Julien Cicero, Robert-Alain Toillon, Quentin Bailleul, Luca Visentin, Federico Alessandro Ruffinatti, Guillaume Brysbaert, Marc F Lensink, Jerome De Ruyck, Anna Rita Cantelmo, Alessandra Fiorio Pla, Dimitra Gkika
TRPC3 shapes the ER-mitochondria Ca<sup>2+</sup> transfer characterizing tumour-promoting senescence - (le 18/02/2022)
Cellular senescence is implicated in a great number of diseases including cancer. Although alterations in mitochondrial metabolism were reported as senescence drivers, the underlying mechanisms remain elusive. We report the mechanism altering mitochondrial function and OXPHOS in stress-induced senescent fibroblasts. We demonstrate that TRPC3 protein, acting as a controller of mitochondrial Ca^(2+) load via negative regulation of IP(3) receptor-mediated Ca^(2+) release, is down regulated in...
- Valerio Farfariello, Dmitri V Gordienko, Lina Mesilmany, Yasmine Touil, Emmanuelle Germain, Ingrid Fliniaux, Emilie Desruelles, Dimitra Gkika, Morad Roudbaraki, George Shapovalov, Lucile Noyer, Mathilde Lebas, Laurent Allart, Nathalie Zienthal-Gelus, Oksana Iamshanova, Franck Bonardi, Martin Figeac, William Laine, Jerome Kluza, Philippe Marchetti, Bruno Quesnel, Daniel Metzger, David Bernard, Jan B Parys, Loïc Lemonnier, Natalia Prevarskaya
Put in a "Ca<sup>2+</sup>ll" to Acute Myeloid Leukemia - (le 15/02/2022)
Acute myeloid leukemia (AML) is a clonal disorder characterized by genetic aberrations in myeloid primitive cells (blasts) which lead to their defective maturation/function and their proliferation in the bone marrow (BM) and blood of affected individuals. Current intensive chemotherapy protocols result in complete remission in 50% to 80% of AML patients depending on their age and the AML type involved. While alterations in calcium signaling have been extensively studied in solid tumors, little...
- Clara Lewuillon, Marie-Océane Laguillaumie, Bruno Quesnel, Thierry Idziorek, Yasmine Touil, Loïc Lemonnier
Pairing cells of different sizes in a microfluidic device for immunological synapse monitoring - (le 31/01/2022)
Analyzing cell-cell interaction is essential to investigate how immune cells function. Elegant designs have been demonstrated to study lymphocytes and their interaction partners. However, these devices have been targeting cells of similar dimensions. T lymphocytes are smaller, more deformable, and more sensitive to pressure than many cells. This work aims to fill the gap of a method for pairing cells with different dimensions. The developed method uses hydrodynamic flow focusing in the...
- Faruk Azam Shaik, Clara Lewuillon, Aurélie Guillemette, Bahram Ahmadian, Carine Brinster, Bruno Quesnel, Dominique Collard, Yasmine Touil, Loïc Lemonnier, Mehmet Cagatay Tarhan
The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a divalent cations permeant channel but also has intrinsic serine/threonine kinase activity. It is ubiquitously expressed in normal tissues and studies have indicated that it participates in important physiological and pharmacological processes through its channel-kinase activity, such as calcium/magnesium homeostasis, phosphorylation of proteins involved in embryogenesis or the cellular process. Accumulating evidence has...
- Clément Cordier, Natalia Prevarskaya, V'yacheslav Lehen'kyi
3-phosphoinositide-dependent protein kinase 1 (PDK1) mediates crosstalk between Src and Akt pathways in MET receptor signaling - (le 22/09/2021)
The high-affinity tyrosine kinase receptor MET plays a pivotal role in several facets of cell regulation. Although its mitogenic effect is well documented, some aspects of connection patterns between signaling pathways involved in cell cycle progression remain to be deciphered. We have used a tractable heterologous expression system, the Xenopus oocyte, to detect connections between distinct MET signaling cascades involved in G2/M progression. Our results reveal that Src acts as an adapter via...
- Caroline Molinaro, Alain Martoriati, Arlette Lescuyer, Ingrid Fliniaux, David Tulasne, Katia Cailliau