Publications by authors named "Jean-Francois Cote"

Article Synopsis
  • The hGID complex functions as an important E3 ligase influencing various cellular processes, such as the cell cycle and metabolism, but its full range of biological roles is not well understood.
  • Researchers utilized the BioID2 technique to discover proteins that interact with the hGID complex, identifying ARHGAP11A as a substrate that is ubiquitinated by GID4, leading to its degradation.
  • Inhibiting GID4 or depleting it raises ARHGAP11A levels, impacting cell motility and migration, as ARHGAP11A affects RhoA activity at the cell's edge.
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Unlabelled: Halting breast cancer metastatic relapses following primary tumor removal and the clinical dormant phase, remains challenging, due to a lack of specific vulnerabilities to target during dormancy. To address this, we conducted genome-wide CRISPR screens on two breast cancer cell lines with distinct dormancy properties: 4T1 (short-term dormancy) and 4T07 (prolonged dormancy). We discovered that loss of class-III PI3K, Pik3c3, revealed a unique vulnerability in 4T07 cells.

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Growth arrest-specific 6 (GAS6) is a secreted protein that acts as a ligand for TAM receptors (TYRO3, AXL, and MERTK). In humans, GAS6 circulating levels and genetic variations in GAS6 are associated with hyperglycemia and increased risk of type 2 diabetes. However, the mechanisms by which GAS6 influences glucose metabolism are not understood.

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Clinical practice and clinical research heavily rely on primary tumors, circulating tumor DNA, and/or overt metastases as sources of material for predicting or investigating breast cancer metastatic relapses. However, these approaches do not consider emerging fundamentals in the biology of metastatic dormancy and relapse. Conversely, the field of metastatic dormancy often discounts key clinical factors influencing relapse dynamics (e.

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Article Synopsis
  • The study explores the interactome of 28 ARF and ARL GTPases using a method called BioID, uncovering around 3000 high-confidence interacting proteins.
  • New localizations for ARL4D and ARL10 were identified, along with a unique expression pattern for ARL14 in the stomach and intestines.
  • Functional assays showed that ARL14 can activate PLD1 and play a role in cargo trafficking via the ESCPE-1 complex, contributing to understanding ARF and ARL functions in cellular processes.
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The ubiquitin proteasome system performs the covalent attachment of lysine 48-linked polyubiquitin chains to substrate proteins, thereby targeting them for degradation, while deubiquitylating enzymes (DUBs) reverse this process. This posttranslational modification regulates key features both of innate and adaptative immunity, including antigen presentation, protein homeostasis and signal transduction. Here we show that loss of one of the most highly expressed DUBs, Otub1, results in changes in murine splenic B cell subsets, leading to a significant increase in marginal zone and transitional B cells and a concomitant decrease in follicular B cells.

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Purpose: A re-transurethral resection of the bladder (re-TURB) is a well-established approach in managing non-muscle invasive bladder cancer (NMIBC) for various reasons: repeat-TURB is recommended for a macroscopically incomplete initial resection, restaging-TURB is required if the first resection was macroscopically complete but contained no detrusor muscle (DM) and second-TURB is advised for all completely resected T1-tumors with DM in the resection specimen. This study assessed the long-term outcomes after repeat-, second-, and restaging-TURB in T1-NMIBC patients.

Methods: Individual patient data with tumor characteristics of 1660 primary T1-patients (muscle-invasion at re-TURB omitted) diagnosed from 1990 to 2018 in 17 hospitals were analyzed.

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Interstrand DNA cross-links (ICLs) represent complex lesions that compromise genomic stability. Several pathways have been involved in ICL repair, but the extent of factors involved in the resolution of ICL-induced DNA double-strand breaks (DSBs) remains poorly defined. Using CRISPR-based genomics, we identified FIGNL1 interacting regulator of recombination and mitosis (FIRRM) as a sensitizer of the ICL-inducing agent mafosfamide.

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Epithelial-to-mesenchymal transition (EMT) plays a crucial role in metastasis, which is the leading cause of death in breast cancer patients. Here, we show that Cdc42 GTPase-activating protein (CdGAP) promotes tumor formation and metastasis to lungs in the HER2-positive (HER2) murine breast cancer model. CdGAP facilitates intravasation, extravasation, and growth at metastatic sites.

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(1) Background: This article discusses the first two phases of development and validation of the Three Domains of Judgment Test (3DJT). This computer-based tool, co-constructed with users and capable of being administered remotely, aims to assess the three main domains of judgment (practical, moral, and social) and learn from the psychometric weaknesses of tests currently used in clinical practice. (2) Method: First, we presented the 3DJT to experts in cognition, who evaluated the tool as a whole as well as the content validity, relevance, and acceptability of 72 scenarios.

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Article Synopsis
  • The study looked at ARF and ARL proteins, which are important "switches" in cells that help control different actions and functions.
  • Researchers used a special method to find out how these proteins interact with nearly 3,000 other molecules in cells, discovering new locations for some proteins like ARL4D and ARL10.
  • They also found that a less known protein called ARL14 is mainly found in the stomach and intestines, and it helps activate another molecule, PLD1, that plays a role in moving things around inside the cells.
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In developing embryos, specific cell populations are often removed to remodel tissue architecture for organogenesis. During urinary tract development, an epithelial duct called the common nephric duct (CND) gets shortened and eventually eliminated to remodel the entry point of the ureter into the bladder. Here we show that non-professional efferocytosis (the process in which epithelial cells engulf apoptotic bodies) is the main mechanism that contributes to CND shortening.

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Background: Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC) is a relatively rare diagnosis with an ambiguous character owing to the presence of an aggressive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive.

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  • Myoblast fusion is important for making strong muscle fibers that have more than one nucleus!
  • Researchers studied proteins like DOCK1 and Elmo2 that help with myoblast fusion, finding that changes in the Elmo2 gene affected how well myoblasts fused!
  • By changing Elmo2 to a certain form, they were able to improve muscle repair in a mouse model of muscular dystrophy, showing potential for treating muscle diseases in the future!
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Article Synopsis
  • Homologous recombination (HR) is crucial for repairing DNA double strand breaks and managing replication stress to maintain genome stability and prevent cancer.
  • The study focuses on mammalian RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3), revealing their roles in both DNA repair and the resolution of stalled replication forks, while also uncovering their interaction with RNA metabolic pathways using the BioID approach.
  • The findings suggest that these RAD51 paralogs have novel functions in cell biology that could serve as potential biomarkers for breast cancer prognosis, as their RNA expression is linked to poorer patient outcomes.
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Article Synopsis
  • DOCK proteins are guanine nucleotide exchange factors (GEFs) that activate RHO GTPases CDC42 and RAC1, playing a key role in controlling various cellular processes.
  • There are four subfamilies of DOCK proteins (A to D), each with different affinities for CDC42 and RAC1, and some are associated with ELMO proteins that auto-inhibit their activity.
  • Structural studies have improved our understanding of how DOCK proteins function, including mechanisms of nucleotide exchange and regulation, which is crucial for developing targeted therapies for diseases linked to DOCK GEFs.
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Multiple factors act in concert to define the fate of disseminated tumor cells (DTC) to enter dormancy or develop overt metastases. Here, we review these factors in the context of three stages of the metastatic cascade that impact DTCs. First, cells can be programmed within the primary tumor microenvironment to promote or inhibit dissemination, and the primary tumor can condition a premetastatic niche.

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Background: The pathological existence and clinical consequence of stage T1 grade 1 (T1G1) bladder cancer are the subject of debate. Even though the diagnosis of T1G1 is controversial, several reports have consistently found a prevalence of 2-6% G1 in their T1 series. However, it remains unclear if T1G1 carcinomas have added value as a separate category to predict prognosis within the non-muscle-invasive bladder cancer (NMIBC) spectrum.

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At mitotic entry, reorganization of the actomyosin cortex prompts cells to round-up. Proteins of the ezrin, radixin, and moesin family (ERM) play essential roles in this process by linking actomyosin forces to the plasma membrane. Yet, the cell-cycle signal that activates ERMs at mitotic entry is unknown.

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The receptor tyrosine kinase AXL is emerging as a key player in tumor progression and metastasis and its expression correlates with poor survival in a plethora of cancers. While studies have shown the benefits of AXL inhibition for the treatment of metastatic cancers, additional roles for AXL in cancer progression are still being explored. This review discusses recent advances in understanding AXL's functions in different tumor compartments including cancer, vascular, and immune cells.

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Article Synopsis
  • Proximity-dependent biotinylation (BioID) is a technique used to identify protein interactions that are often difficult to capture using traditional methods, focusing on transient and weak interactions in specific locations.
  • The text outlines the essential steps and a detailed protocol for conducting BioID experiments in mammalian cells, ensuring reproducibility and accuracy.
  • It also covers the mass spectrometry methods and bioinformatics analyses necessary for interpreting the data collected during these experiments, referencing a study for in-depth guidance.
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Article Synopsis
  • - The study focuses on improving the management of muscle-invasive bladder cancer by predicting how patients will respond to neoadjuvant chemotherapy (NAC), as non-responders may face unnecessary treatment side effects.
  • - Researchers analyzed tissue samples using mid-infrared imaging to assess the treatment response, scoring pixels of the tissue based on their response to chemotherapy, validated through histopathological examination.
  • - The findings revealed that despite visual uniformity in tumor samples, spectral analysis using mid-infrared imaging could identify significant metabolic differences, laying the groundwork for better predicting chemotherapy responses in patients.
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