MCL-1 as a molecular switch between myofibroblastic and pro-angiogenic features of breast cancer-associated fibroblasts.

Breast cancer-associated fibroblasts (bCAFs) comprise inflammatory CAFs (iCAFs), characterized by the secretion of pro-inflammatory cytokines, and myofibroblastic CAFs (myCAFs), distinguished by their high production of extracellular matrix and their immunosuppressive properties. We previously showed that targeting the anti-apoptotic protein MCL-1 in primary culture of bCAF derived directly from human samples reduces their myofibroblastic characteristics. We herein show by single-cell RNA-sequencing analysis of bCAFs that MCL-1 knock down induces a phenotypic shift from wound-myCAF to IL-iCAF, characterized by the upregulation of genes associated with inflammation as well as angiogenesis-related genes.

A DIA-MS-based proteomics approach to find potential serum prognostic biomarkers in glioblastoma patients.

No blood-based protein biomarkers are currently available for routine clinical use to determine the prognosis of patients with glioblastoma (GB). We performed data-independent acquisition mass spectrometry (DIA-MS)-based proteomics on 96 presurgical serum samples from patients with GB and 30 serum samples from healthy controls to identify such markers. Among the 622 serum proteins differentially expressed between the GB and control groups, 191 had a |log(fold change)| ≥ 0.

A Novel Function of Na Channel β3 Subunit in Endothelial Cell Alignment Through Autophagy Modulation.

Endothelial cells (EC) play a pivotal role in vascular homeostasis. By sensing shear stress generated by blood flow, EC endorse vasculoprotection through mechanotransduction signaling pathways. Various ion channels are involved in mechanosignaling, and here, we investigated the endothelial voltage-gated Na channels (Na channels), since their mechanosensitivity has been previously demonstrated in cardiomyocytes.

Secretomes From Non-Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial-to-Mesenchymal Transition.

Aim: The tumor microenvironment (TME) of non-small cell lung cancer (NSCLC) is highly heterogeneous and is involved in tumorigenesis and resistance to therapy. Among the cells of the TME, endothelial cells are associated with the latter processes through endothelial-to-mesenchymal transition (EndMT). During EndMT, endothelial cells (ECs) progressively lose their endothelial phenotype in favor of a mesenchymal phenotype, which favors the production of cancer-associated fibroblasts (CAFs).

Proteomics of tumor and serum samples from isocitrate dehydrogenase-wildtype glioblastoma patients: is the detoxification of reactive oxygen species associated with shorter survival?

Proteomics has been little used for the identification of novel prognostic and/or therapeutic markers in isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GB). In this study, we analyzed 50 tumor and 30 serum samples from short- and long-term survivors of IDH-wildtype GB (STS and LTS, respectively) by data-independent acquisition mass spectrometry (DIA-MS)-based proteomics, with the aim of identifying such markers. DIA-MS identified 5422 and 826 normalized proteins in tumor and serum samples, respectively, with only three tumor proteins and 26 serum proteins displaying significant differential expression between the STS and LTS groups.

Proteomic analysis of SARS-CoV-2 particles unveils a key role of G3BP proteins in viral assembly.

Considerable progress has been made in understanding the molecular host-virus battlefield during SARS-CoV-2 infection. Nevertheless, the assembly and egress of newly formed virions are less understood. To identify host proteins involved in viral morphogenesis, we characterize the proteome of SARS-CoV-2 virions produced from A549-ACE2 and Calu-3 cells, isolated via ultracentrifugation on sucrose cushion or by ACE-2 affinity capture.

Macrophage-infectivity potentiator of (TcMIP) is a new pro-type 1 immuno-stimulating protein for neonatal human cells and vaccines in mice.

This work identifies the protein "macrophage infectivity potentiator" of trypomastigotes, as supporting a new property, namely a pro-type 1 immunostimulatory activity on neonatal cells. In its recombinant form (rTcMIP), this protein triggers the secretion of the chemokines CCL2 and CCL3 by human umbilical cord blood cells from healthy newborns, after 24h culture. Further stimulation for 72h results in secretion of IFN-γ, provided cultures are supplemented with IL-2 and IL-18.

First Identification of a Large Set of Serine Hydrolases by Activity-Based Protein Profiling in Dibutyl Phthalate-Exposed Zebrafish Larvae.

Despite the involvement of several serine hydrolases (SHs) in the metabolism of xenobiotics such as dibutyl phthalate (DBP), no study has focused on mapping this enzyme class in zebrafish, a model organism frequently used in ecotoxicology. Here, we survey and identify active SHs in zebrafish larvae and search for biological markers of SH type after exposure to DBP. Zebrafish were exposed to 0, 5, and 100 µg/L DBP from 4 to 120 h post-fertilization.

Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosis.

Hereditary xerocytosis is a dominant red cell membrane disorder characterized by an increased leak of potassium from the inside to outside the red blood cell membrane, associated with loss of water leading to red cell dehydration and chronic hemolysis. 90% of cases are related to heterozygous gain of function mutations in PIEZO1, encoding a mechanotransductor that translates a mechanical stimulus into a biological signaling. Data are still required to understand better PIEZO1-HX pathophysiology.

Impact of Fetal Growth Restriction on the Neonatal Microglial Proteome in the Rat.

Microglial activation is a key modulator of brain vulnerability in response to intra-uterine growth restriction (IUGR). However, the consequences of IUGR on microglial development and the microglial proteome are still unknown. We used a model of IUGR induced by a gestational low-protein diet (LPD) in rats.

RAB10 Interacts with ABCB4 and Regulates Its Intracellular Traffic.

ABCB4 (ATP-binding cassette subfamily B member 4) is an ABC transporter expressed at the canalicular membrane of hepatocytes where it ensures phosphatidylcholine secretion into bile. Genetic variations of ABCB4 are associated with several rare cholestatic diseases. The available treatments are not efficient for a significant proportion of patients with ABCB4-related diseases and liver transplantation is often required.

Comprehensive Analysis of Transcript and Protein Relative Abundance During Blood Stages of Infection.

is the main causative agent of human malaria. During the intraerythrocytic development cycle, the morphology changes dramatically from circulating young rings to sequestered mature trophozoites and schizonts. Sequestered forms contribute to the pathophysiology of severe malaria as the infected erythrocytes obstruct the microvascular flow in deep organs and induce local inflammation.

Lkb1 suppresses amino acid-driven gluconeogenesis in the liver.

Excessive glucose production by the liver is a key factor in the hyperglycemia observed in type 2 diabetes mellitus (T2DM). Here, we highlight a novel role of liver kinase B1 (Lkb1) in this regulation. We show that mice with a hepatocyte-specific deletion of Lkb1 have higher levels of hepatic amino acid catabolism, driving gluconeogenesis.

Mutation Modifies Exportin 1 Localisation and Interactome in B-cell Lymphoma.

The gene encodes exportin 1 (XPO1) that controls the nuclear export of cargo proteins and RNAs. Almost 25% of primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) cases harboured a recurrent point mutation (NM_003400, chr2:g61718472C>T) resulting in the E571K substitution within the hydrophobic groove of the protein, the site of cargo binding. We investigated the impact of the mutation using PMBL/cHL cells having various statuses and CRISPR-Cas9-edited cells in which the E571K mutation was either introduced or knocked-out.

p53 activation during ribosome biogenesis regulates normal erythroid differentiation.

The role of ribosome biogenesis in erythroid development is supported by the recognition of erythroid defects in ribosomopathies in both Diamond-Blackfan anemia and 5q- syndrome. Whether ribosome biogenesis exerts a regulatory function on normal erythroid development is still unknown. In the present study, a detailed characterization of ribosome biogenesis dynamics during human and murine erythropoiesis showed that ribosome biogenesis is abruptly interrupted by the decline in ribosomal DNA transcription and the collapse of ribosomal protein neosynthesis.

Pairing MCL-1 inhibition with venetoclax improves therapeutic efficiency of BH3-mimetics in AML.

Objectives: Venetoclax combined with hypomethylating agents is a new therapeutic strategy frequently used for treating AML patients who are not eligible for conventional chemotherapy. However, high response rates are heterogeneous due to different mechanisms mediating resistance to venetoclax such as up-regulation of MCL-1 expression. We thus tested the anti-leukemic activity of S63845, a specific MCL-1 inhibitor.