• Deciphering genetic and nongenetic factors underlying tumour dormancy: insights from multiomics analysis of two syngeneic MRD models of melanoma and leukemia - (le 02/09/2024)

    CONCLUSIONS: Our study underscores the complexity of tumour dormancy, implicating both genetic and nongenetic factors. By comparing genomic, transcriptomic, proteomic, and epigenomic datasets, our study provides a comprehensive understanding of the molecular landscape of minimal residual disease. These results provide a robust foundation for forthcoming investigations and offer potential avenues for the advancement of targeted MRD therapies in leukemia and melanoma patients, emphasizing the...

    • Marie-Océane Laguillaumie, Sofia Titah, Aurélie Guillemette, Bernadette Neve, Frederic Leprêtre, Pascaline Ségard, Faruk Azam Shaik, Dominique Collard, Jean-Claude Gerbedoen, Léa Fléchon, Lama Hasan Bou Issa, Audrey Vincent, Martin Figeac, Shéhérazade Sebda, Céline Villenet, Jérôme Kluza, William Laine, Isabelle Fournier, Jean-Pascal Gimeno, Maxence Wisztorski, Salomon Manier, Mehmet Cagatay Tarhan, Bruno Quesnel, Thierry Idziorek, Yasmine Touil

  • Integrated single-cell RNA-seq analysis reveals mitochondrial calcium signaling as a modulator of endothelial-to-mesenchymal transition - (le 09/08/2024)

    Endothelial cells (ECs) are highly plastic, capable of differentiating into various cell types. Endothelial-to-mesenchymal transition (EndMT) is crucial during embryonic development and contributes substantially to vascular dysfunction in many cardiovascular diseases (CVDs). While targeting EndMT holds therapeutic promise, understanding its mechanisms and modulating its pathways remain challenging. Using single-cell RNA sequencing on three in vitro EndMT models, we identified conserved gene...

    • Mathilde Lebas, Giorgia Chinigò, Evan Courmont, Louay Bettaieb, Amani Machmouchi, Jermaine Goveia, Aleksandar Beatovic, Job Van Kerckhove, Cyril Robil, Fabiola Silva Angulo, Mauro Vedelago, Alina Errerd, Lucas Treps, Vance Gao, Hilda C Delgado De la Herrán, Alicia Mayeuf-Louchart, Laurent L'homme, Mohamed Chamlali, Camille Dejos, Valérie Gouyer, Venkata Naga Srikanth Garikipati, Dhanendra Tomar, Hao Yin, Hajime Fukui, Stefan Vinckier, Anneke Stolte, Lena-Christin Conradi, Fabrice Infanti, Loic Lemonnier, Elisabeth Zeisberg, Yonglun Luo, Lin Lin, Jean-Luc Desseyn, J Pickering, Raj Kishore, Muniswamy Madesh, David Dombrowicz, Fabiana Perocchi, Bart Staels, Alessandra Fiorio Pla, Dimitra Gkika, Anna Rita Cantelmo

  • Tumor Microenvironment Modulates Invadopodia Activity of Non-Selected and Acid-Selected Pancreatic Cancer Cells and Its Sensitivity to Gemcitabine and C18-Gemcitabine - (le 10/05/2024)

    CONCLUSIONS: We propose C18 as a more effective approach to conventional GEM in developing new therapeutic strategies overcoming PDAC chemoresistance.

    • Tiago M A Carvalho, Madelaine Magalì Audero, Maria Raffaella Greco, Marilena Ardone, Teresa Maggi, Rosanna Mallamaci, Barbara Rolando, Silvia Arpicco, Federico Alessandro Ruffinatti, Alessandra Fiorio Pla, Natalia Prevarskaya, Tomas Koltai, Stephan J Reshkin, Rosa Angela Cardone

  • Converting cell death into senescence by PARP1 inhibition improves recovery from acute oxidative injury - (le 09/05/2024)

    Excessive amounts of reactive oxygen species (ROS) lead to macromolecular damage and high levels of cell death with consequent pathological sequelae. We hypothesized that switching cell death to a tissue regenerative state could potentially improve the short-term and long-term detrimental effects of ROS-associated acute tissue injury, although the mechanisms regulating oxidative stress-induced cell fate decisions and their manipulation for improving repair are poorly understood. Here, we show...

    • Jamil Nehme, Lina Mesilmany, Marta Varela-Eirin, Simone Brandenburg, Abdullah Altulea, Yao Lin, Mariana Gaya da Costa, Marc Seelen, Jan-Luuk Hillebrands, Harry van Goor, Raya Saab, Haidar Akl, Natacha Prevarskaya, Valerio Farfariello, Marco Demaria

  • NLRP6 controls pulmonary inflammation from cigarette smoke in a gut microbiota-dependent manner - (le 26/12/2023)

    Chronic obstructive pulmonary disease (COPD) is a major health issue primarily caused by cigarette smoke (CS) and characterized by breathlessness and repeated airway inflammation. NLRP6 is a cytosolic innate receptor controlling intestinal inflammation and orchestrating the colonic host-microbial interface. However, its roles in the lungs remain largely unexplored. Using CS exposure models, our data show that airway inflammation is strongly impaired in Nlrp6-deficient mice with drastically fewer...

    • Mégane Nascimento, Sarah Huot-Marchand, Manoussa Fanny, Marjolène Straube, Marc Le Bert, Florence Savigny, Lionel Apetoh, Jacques Van Snick, Fabrice Trovero, Mathias Chamaillard, Valérie F J Quesniaux, Bernhard Ryffel, Philippe Gosset, Aurélie Gombault, Nicolas Riteau, Harry Sokol, Isabelle Couillin

  • Synthesis and Biological Activity of a New Indenoisoquinoline Copper Derivative as a Topoisomerase I Inhibitor - (le 14/10/2023)

    Topoisomerases are interesting targets in cancer chemotherapy. Here, we describe the design and synthesis of a novel copper(II) indenoisoquinoline complex, WN198. The new organometallic compound exhibits a cytotoxic effect on five adenocarcinoma cell lines (MCF-7, MDA-MB-231, HeLa, HT-29, and DU-145) with the lowest IC(50) (0.37 ± 0.04 μM) for the triple-negative MDA-MB-231 breast cancer cell line. Below 5 µM, WN198 was ineffective on non-tumorigenic epithelial breast MCF-10A cells and Xenopus...

    • Caroline Molinaro, Nathalie Wambang, Sylvain Pellegrini, Natacha Henry, Marc F Lensink, Emmanuelle Germain, Till Bousquet, Jérôme de Ruyck, Katia Cailliau, Lydie Pélinski, Alain Martoriati

  • 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

  • NR1D1 controls skeletal muscle calcium homeostasis through myoregulin repression - (le 02/08/2022)

    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