Biology subjects

Leblanc, R.

Publications and source records attributed to Leblanc, R..

6 recordsLinked to original sources

bioRxiv2026

ADAM10 tailors extracellular vesicles for content transfer rather than signaling by contact

Etxtracellular vesicles (EVs) support cell-to-cell communication, both in physiological and pathological contexts and emerge as new biomarkers and potential therapeutics. Yet, despite EVs holding huge promises, our understanding of core mechanisms governing EV signaling remains significantly underdeveloped. Our previous work indicated that syndecans and their cytosolic adaptor syntenin control the biogenesis of a major subset of small EVs (sEVs). Here we show that syndecans control the accumulation of ADAM10 into sEVs. ADAM10 promotes the formation of sEVs enriched in cleaved receptors (reducing sEV corona), supports the sorting of proteins with intracellular functions, and tailors sEVs for the delivery of their internal content, e.g. syntenin, into the cytosol of recipient cells. Conversely, inhibition of ADAM10 favors the production of sEVs bearing full-length, signaling-competent receptors/ligands and enhances contact-dependent signaling. These findings uncover a protease-regulated switch that tailors sEV composition and signaling modality, providing important new mechanistic insights into the core molecular pathways supporting EV-mediated communication.

cell biology↗

bioRxiv2025

Syntenin orchestrates matrix degradation by controlling MT1-MMP secretion in small extracellular vesicles and invadopodia formation

Extracellular matrix (ECM) remodelling is essential for tumour progression. The metalloproteinase MT1-MMP promotes cell invasion by degrading ECM components. MT1-MMP accumulates at invadopodia, actin-rich structures mediating ECM degradation, and is also present on the surface of small extracellular vesicles (sEV), key players in cell-to-cell communication. The role of sEV-associated MT1-MMP in ECM degradation and the mechanisms supporting MT1-MMP loading into sEV are unknown. We previously established that the syntenin PDZ protein, in association with the syndecan (SDC), is essential for sEV from endosomal origin biogenesis. In the present study, we demonstrate that syntenin contributes to ECM degradation via invadopodia in MDA-MB-231 triple negative breast cancer (TNBC) cells, whereas SDC limit it. Moreover, we identify that syntenin colocalizes with MT1-MMP in late endosomes and directly interacts with MT1-MMP. Furthermore, we decipher that both syntenin and SDC are essential for the specific loading of MT1-MMP into sEV. Additionally, we show that sEV-mediated ECM degradation depends on MT1-MMP activity and syntenin. Our findings show how syntenin-SDC-MT1-MMP complexes orchestrate ECM degradation and pave the way for innovative rational approaches to control TNBC invasion.

cancer biology↗

bioRxiv2025

Lysophosphatidic acid controls autotaxin binding to 1-integrin: impact on disease progression in murine collagen-induced arthritis.

Autotaxin (ATX) is a lysophospholipase D (lysoPLD) serving as both a lysophosphatidic acid (LPA)-producing enzyme and a LPA docking molecule. ATX binds to the cell surface via interaction with adhesive molecules, including {beta}1-integrin, potentially facilitating LPA access to its specific G protein-coupled receptors. However, the precise protein-protein interaction sequences and their biological implications remain unknown. Here, we identify the interaction domains between ATX and {beta}1-integrin and generate specific blocking antibodies allowing to demonstrate that ATX-{beta}1 binding domain involves a cryptic epitope unmasked by LPA docking. In addition, whereas anti-ATX antibodies do not inhibit the lysoPLD activity, immunological neutralization of the ATX-{beta}1 integrin binding site reduces arthritis development in a collagen-induced arthritis model. These findings offer novel insights into the molecular mechanisms governing ATX functions, which, in addition to its enzymatic activity, requires cell surface binding. These findings suggest that ATX binding domains could be targeted for novel therapeutic approaches.

cell biology↗

bioRxiv2023

Downregulation of stromal syntenin sustains AML development

The crosstalk between cancer and stromal cells plays a critical role in tumor progression. Syntenin is a small scaffold protein involved in the regulation of intercellular communication that is emerging as a target for cancer therapy. Here, we show that certain aggressive forms of acute myeloid leukemia (AML) reduce the expression of syntenin in bone marrow stromal cells (BMSC), stromal syntenin deficiency, in turn, generating a pro-tumoral microenvironment. From serial transplantations in mice and co-culture experiments, we conclude that syntenin-deficient BMSC stimulate AML aggressiveness by promoting AML cell survival and protein synthesis. This pro-tumoral activity is supported by increased expression of endoglin, a classical marker of BMSC, which in trans stimulates AML translational activity. In short, our study reveals a vicious signaling loop potentially at the heart of AML-stroma crosstalk and unsuspected tumor-suppressive effects of syntenin that need to be considered during systemic targeting of syntenin in cancer therapy.

cancer biology↗

bioRxiv2021

A syntenin-deficient microenvironment educates AML for aggressiveness

In acute myeloid leukemia (AML), the stromal microenvironment plays a prominent role in promoting tumor cell survival and progression. Although widely explored, the crosstalk between leukemic and stromal cells remains poorly understood. Syntenin, a multi-domain PDZ protein, controls both the trafficking and signaling of key molecules involved in intercellular communication. Therefore, we aimed to clarify the role of environmental syntenin in the progression of AML. By in vivo approaches in syngeneic mice, we demonstrate that a syntenin-deficient environment reprograms AML blasts to survive independently of the stroma. Up-regulation of EEF1A2 in the blasts controls this gain of cell survival. Furthermore, using ex vivo co-culture systems, we show that syntenin-deficient bone marrow stromal cells (BMSC) enhance the survival of different types of AML cells, including patient samples, and suffice to educate syngeneic AML, recapitulating micro-environmental effects observed in vivo. We establish that syntenin-deficiency causes an increase of eIF5A and autophagy-related factors in BMSC, and provide evidence that the inhibition of autophagy prevents syntenin-deficient BMSC to stimulate AML survival. Altogether, these findings indicate that host-syntenin in the BM microenvironment acts as a repressor of AML aggressiveness. Key points- A syntenin-deficient host reprograms AML blasts, enhancing total protein synthesis and cell survival pathways - Autophagy in the syntenin-deficient microenvironment is responsible for the gain of AML cell survival

cancer biology↗

bioRxiv2020

Carbon dots deposition in adult bones reveal areas of growth, injury and regeneration

C-dots synthesized from carbon nanopowder (oxidation, hydrothermal) are particularly attractive theragnostic agents for bone-related injuries and disease due to their bright fluorescence and high binding affinity and specificity for bones, as demonstrated in a larval animal model. Larval bone development, however, is significantly different from the bone growth, repair and regeneration processes occurring in adults. Using adult zebrafish, we investigated C-dots interactions with adult skeletal structures. Upon injection, C-dots were observed at the surface of bones, at sites of appositional growth. In regenerating bones, C-dots were observed at the core and on the surface of the bones depending on the age of the tissue. C-dots deposition occurred within 30 min of delivery and it was highly selective. Importantly, their deposition did not interfere with bone regeneration or the animals health. Together, these properties establish C-dots as novel tools for the diagnostic and treatment of adult bone-related injuries and diseases.

pharmacology and toxicology↗