Hck signaling drives long-distance ECM degradation through endo-exocytosis coupling in macrophages.
- 1Institute for Advanced Biosciences, Centre de Recherche Universite Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, France
Abstract
The diversity of strategies implicated in extracellular matrix (ECM) degradation supporting cell invasion has been poorly achieved. Unlike invasive breast cancer cells, which predominantly degrade the ECM locally via an invadosome-associated degradation, dynamic quantification of live imaging of degradation of physiological ECM such as fibrinogen showed that macrophages employ different modes of ECM degradation since digesting ECM both locally and at long distance. Long distance degradation occurring in macrophage is dependent on both matrix metalloproteases (MMPs) and cathepsins release. Optogenetic manipulation showed that HCK signaling specifically regulates positively this new mode of fibrinogen degradation by increasing cathepsins release and activating localized fusion of acidic CD63-endolysosome vesicles at the vicinity of clathrin hotspots at the rear of macrophages, appearing as a new exo-endocytosis coupling. Computational biology and in silico simulations support the importance of the fine spatiotemporal coordination between MMPs and cathepsin activities, and regulation of cathepsin activity by local acid release. Different mode of ECM degradation can thus coexist and this highlight the importance of understanding the cathepsins-MMPs synergy in shaping invasive behavior across different physio-pathological invasion processes.
Related
- P2Y6 signaling selectively regulates TLR3-induced chemokine release in murine bone marrow-derived macrophages, with opposing effects on CCL2 and CXCL1
- Developmental IL7/IL7R signaling in fetal resident tissue macrophages regulates adaptive responses to liver injury
- Anti-inflammatory macrophages limit endothelial inflammation and restrict neutrophil recruitment through Gas6/AXL signaling
- Senkyunolide I Inhibits mtDNA‐cGAS‐STING Signaling in Macrophages via Targeting VDAC1 Oligomerization to Attenuate Ulcerative Colitis
- Cyclooxygenase-mediated IL-10Rα signaling underlies pro-tumor phenotypes of macrophages in glioma.
BibTeX
@misc{torrestorres2026signaling,
title = {{Hck signaling drives long-distance ECM degradation through endo-exocytosis coupling in macrophages.}},
author = {C. Cristina Torres-Torres and M. Ruscone and S. B. Morparthi and L. CAMPOS PERELLO and A.-P. Bouin and F. Senger and I. Bourrin-Reynard and C. ODDOU and V. PAKULSKA and Y. Coute and A. Grichine and L. Calzone and S. Vassilopoulos and E. PLANUS and O. Destaing},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.749091},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749091v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Hck signaling drives long-distance ECM degradation through endo-exocytosis coupling in macrophages.
AU - C. Cristina Torres-Torres
AU - M. Ruscone
AU - S. B. Morparthi
AU - L. CAMPOS PERELLO
AU - A.-P. Bouin
AU - F. Senger
AU - I. Bourrin-Reynard
AU - C. ODDOU
AU - V. PAKULSKA
AU - Y. Coute
AU - A. Grichine
AU - L. Calzone
AU - S. Vassilopoulos
AU - E. PLANUS
AU - O. Destaing
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.749091
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.749091v1
AB - The diversity of strategies implicated in extracellular matrix (ECM) degradation supporting cell invasion has been poorly achieved. Unlike invasive breast cancer cells, which predominantly degrade the ECM locally via an invadosome-associated degradation, dynamic quantification of live imaging of degradation of physiological ECM such as fibrinogen showed that macrophages employ different modes of ECM degradation since digesting ECM both locally and at long distance. Long distance degradation occurring in macrophage is dependent on both matrix metalloproteases (MMPs) and cathepsins release. Optogenetic manipulation showed that HCK signaling specifically regulates positively this new mode of fibrinogen degradation by increasing cathepsins release and activating localized fusion of acidic CD63-endolysosome vesicles at the vicinity of clathrin hotspots at the rear of macrophages, appearing as a new exo-endocytosis coupling. Computational biology and in silico simulations support the importance of the fine spatiotemporal coordination between MMPs and cathepsin activities, and regulation of cathepsin activity by local acid release. Different mode of ECM degradation can thus coexist and this highlight the importance of understanding the cathepsins-MMPs synergy in shaping invasive behavior across different physio-pathological invasion processes.
ER -