07 / 09 / 2021
Cancer Research
Allosteric inhibition of HER2 by Moesin-mimicking compounds targets HER2-positive cancers and brain metastases
Camille Faure, Rym Djerbi-Bouillié, Anaïs Domingot, Haniaa Bouzinba-Segard, Saïd Taouji,..., Jean-Luc Lenormand, Eric Chevet, Sandrine Bourdoulous
Therapies targeting the tyrosine kinase receptor HER2 have significantly improved survival of HER2+ cancer patients. However, both de novo and acquired resistance remain a challenge, particularly in the brain metastatic setting. Here we report that, unlike other HER tyrosine kinase receptors, HER2 possesses a binding motif in its cytosolic juxtamembrane region that allows interaction with members of the ezrin/radixin/moesin (ERM) family. Under physiological conditions, this interaction controls the localization of HER2 in ERM-enriched domains and stabilizes HER2 in a catalytically repressed state...
23 / 08 / 2021
JID innovations
Deletion of TNFAIP6 Gene in Human Keratinocytes Demonstrates a Role for TSG-6 to Retain Hyaluronan Inside Epidermis
Céline Evrard, Emilie Faway,..., Catherine Lambert de Rouvroit, Yves Poumay
TSG-6 is a soluble protein secreted in the extracellular matrix by various cell types in response to inflammatory stimuli. TSG-6 interacts with extracellular matrix molecules, particularly hyaluronan (HA), and promotes cutaneous wound closure in mice. Between epidermal cells, the discrete extracellular matrix contains HA and a tiny amount of TSG-6. However, challenges imposed to keratinocytes in reconstructed human epidermis revealed strong induction of TSG-6 expression, after exposure to T helper type 2 cytokines to recapitulate the atopic dermatitis phenotype or after fungal infection that causes secretion of cytokines and antimicrobial peptides...
27 / 07 / 2021
PNAS
Arrest of WNT/β-catenin signaling enables the transition from pluripotent to differentiated germ cells in mouse ovaries
Morgane Le Rolle, Filippo Massa, Pam Siggers, Laurent Turchi, Agnès Loubat, Bon-Kyoung Koo, Hans Clevers, Andy Greenfield, Andreas Schedl, Marie-Christine Chaboissier, Anne-Amandine Chassot
01 / 07 / 2021
Cancers (Basel)
Mitochondrial Metabolism in Carcinogenesis and Cancer Therapy
Hadia Moindjie, Sylvie Rodrigues-Ferreira, Clara Nahmias
Carcinogenesis is a multi-step process that refers to transformation of a normal cell into a tumoral neoplastic cell. The mechanisms that promote tumor initiation, promotion and progression are varied, complex and remain to be understood. Studies have highlighted the involvement of oncogenic mutations, genomic instability and epigenetic alterations as well as metabolic reprogramming, in different processes of oncogenesis...
04 / 06 / 2021
Cardiovascular research
Different cardiovascular and pulmonary phenotypes for single- and double-knock-out mice deficient in BMP9 and BMP10
Claire Bouvard, Ly Tu , Martina Rossi , Agnès Desroches-Castan , Nihel Berrebeh, Elise Helfer, Caroline Roelants...
BMP9 and BMP10 mutations were recently identified in patients with pulmonary arterial hypertension (PAH), but their specific roles in the pathogenesis of the disease are still unclear. We aimed to study the roles of BMP9 and BMP10 in cardiovascular homeostasis and pulmonary hypertension using transgenic mouse models deficient in Bmp9 and/or Bmp10.
11 / 05 / 2021
Blood.
GlcNAc is a mast-cell chromatin-remodeling oncometabolite that promotes systemic mastocytosis aggressiveness
Julie Agopian, Quentin Da Costa, Quang Vo Nguyen, Giulia Scorrano, Paraskevi Kousteridou, Min Yuan, Rabie Chelbi,...
Systemic mastocytosis (SM) is a KIT-driven hematopoietic neoplasm characterized by the excessive accumulation of neoplastic mast cells (MCs) in various organs and, mainly, the bone marrow (BM). Multiple genetic and epigenetic mechanisms contribute to the onset and severity of SM. However, little is known to date about the metabolic underpinnings underlying SM aggressiveness, which has thus far impeded the development of strategies to leverage metabolic dependencies when existing KIT-targeted treatments fail. Here, we show that plasma metabolomic profiles were able to discriminate indolent from advanced forms of the disease...