Nature Communications (Apr 2025)
Peripheral positioning of lysosomes supports melanoma aggressiveness
- Katerina Jerabkova-Roda,
- Marina Peralta,
- Kuang-Jing Huang,
- Antoine Mousson,
- Clara Bourgeat Maudru,
- Louis Bochler,
- Ignacio Busnelli,
- Rabia Karali,
- Hélène Justiniano,
- Lucian-Mihai Lisii,
- Philippe Carl,
- Vincent Mittelheisser,
- Nandini Asokan,
- Annabel Larnicol,
- Olivier Lefebvre,
- Hugo Lachuer,
- Angélique Pichot,
- Tristan Stemmelen,
- Anne Molitor,
- Léa Scheid,
- Quentin Frenger,
- Frédéric Gros,
- Aurélie Hirschler,
- François Delalande,
- Emilie Sick,
- Raphaël Carapito,
- Christine Carapito,
- Dan Lipsker,
- Kristine Schauer,
- Philippe Rondé,
- Vincent Hyenne,
- Jacky G. Goetz
Affiliations
- Katerina Jerabkova-Roda
- Tumor Biomechanics
- Marina Peralta
- Tumor Biomechanics
- Kuang-Jing Huang
- Tumor Biomechanics
- Antoine Mousson
- Université de Strasbourg
- Clara Bourgeat Maudru
- Tumor Biomechanics
- Louis Bochler
- Tumor Biomechanics
- Ignacio Busnelli
- Tumor Biomechanics
- Rabia Karali
- Université de Strasbourg
- Hélène Justiniano
- Université de Strasbourg
- Lucian-Mihai Lisii
- Université de Strasbourg
- Philippe Carl
- Université de Strasbourg
- Vincent Mittelheisser
- Tumor Biomechanics
- Nandini Asokan
- Tumor Biomechanics
- Annabel Larnicol
- Tumor Biomechanics
- Olivier Lefebvre
- Tumor Biomechanics
- Hugo Lachuer
- Institut Curie, PSL, CNRS
- Angélique Pichot
- INSERM UMR_S1109
- Tristan Stemmelen
- INSERM UMR_S1109
- Anne Molitor
- INSERM UMR_S1109
- Léa Scheid
- Faculté de Médecine, Université de Strasbourg et Clinique Dermatologique, Hôpitaux Universitaires de Strasbourg
- Quentin Frenger
- INSERM UMR_S1109
- Frédéric Gros
- INSERM UMR_S1109
- Aurélie Hirschler
- Laboratoire de Spectrométrie de Masse Bio-Organique (LSMBO), IPHC, UMR 7178, CNRS, Université de Strasbourg, Infrastructure Nationale de Protéomique ProFI
- François Delalande
- Laboratoire de Spectrométrie de Masse Bio-Organique (LSMBO), IPHC, UMR 7178, CNRS, Université de Strasbourg, Infrastructure Nationale de Protéomique ProFI
- Emilie Sick
- Université de Strasbourg
- Raphaël Carapito
- INSERM UMR_S1109
- Christine Carapito
- Laboratoire de Spectrométrie de Masse Bio-Organique (LSMBO), IPHC, UMR 7178, CNRS, Université de Strasbourg, Infrastructure Nationale de Protéomique ProFI
- Dan Lipsker
- Faculté de Médecine, Université de Strasbourg et Clinique Dermatologique, Hôpitaux Universitaires de Strasbourg
- Kristine Schauer
- Institut Curie, PSL, CNRS
- Philippe Rondé
- Université de Strasbourg
- Vincent Hyenne
- Tumor Biomechanics
- Jacky G. Goetz
- Tumor Biomechanics
- DOI
- https://doi.org/10.1038/s41467-025-58528-5
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 16
Abstract
Abstract Emerging evidence suggests that the function and position of organelles are pivotal for tumor cell dissemination. Among them, lysosomes stand out as they integrate metabolic sensing with gene regulation and secretion of proteases. Yet, how their function is linked to their position and how this controls metastasis remains elusive. Here, we analyze lysosome subcellular distribution in patient-derived melanoma cells and patient biopsies and show that lysosome spreading scales with melanoma aggressiveness. Peripheral lysosomes promote matrix degradation and cell invasion which is directly linked to the lysosomal and cell transcriptional programs. Using chemo-genetical control of lysosome positioning, we demonstrate that perinuclear clustering impairs lysosome secretion, matrix degradation and invasion. Impairing lysosome spreading significantly reduces invasive outgrowth in two in vivo models, mouse and zebrafish. Our study provides a direct demonstration that lysosome positioning controls cell invasion, illustrating the importance of organelle adaptation in carcinogenesis and suggesting its potential utility for diagnosis of metastatic melanoma.