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Peripheral positioning of lysosomes supports melanoma aggressiveness

Author

Listed:
  • Katerina Jerabkova-Roda

    (Tumor Biomechanics
    INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

  • Marina Peralta

    (Tumor Biomechanics
    INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

  • Kuang-Jing Huang

    (Tumor Biomechanics
    INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

  • Antoine Mousson

    (Université de Strasbourg
    Faculté de Pharmacie)

  • Clara Bourgeat Maudru

    (Tumor Biomechanics
    INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

  • Louis Bochler

    (Tumor Biomechanics
    INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

  • Ignacio Busnelli

    (Tumor Biomechanics
    INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

  • Rabia Karali

    (Université de Strasbourg
    Faculté de Pharmacie)

  • Hélène Justiniano

    (Université de Strasbourg
    Faculté de Pharmacie)

  • Lucian-Mihai Lisii

    (Université de Strasbourg
    Faculté de Pharmacie)

  • Philippe Carl

    (Université de Strasbourg
    Faculté de Pharmacie)

  • Vincent Mittelheisser

    (Tumor Biomechanics
    INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

  • Nandini Asokan

    (Tumor Biomechanics
    INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

  • Annabel Larnicol

    (Tumor Biomechanics
    INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

  • Olivier Lefebvre

    (Tumor Biomechanics
    INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

  • Hugo Lachuer

    (CNRS
    Université Paris-Saclay
    Institut Jacques Monod)

  • Angélique Pichot

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Fédération Hospitalo-Universitaire OMICARE)

  • Tristan Stemmelen

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Fédération Hospitalo-Universitaire OMICARE)

  • Anne Molitor

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Fédération Hospitalo-Universitaire OMICARE)

  • Léa Scheid

    (Hôpitaux Universitaires de Strasbourg)

  • Quentin Frenger

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

  • Frédéric Gros

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

  • Aurélie Hirschler

    (Infrastructure Nationale de Protéomique ProFI)

  • François Delalande

    (Infrastructure Nationale de Protéomique ProFI)

  • Emilie Sick

    (Université de Strasbourg
    Faculté de Pharmacie)

  • Raphaël Carapito

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Fédération Hospitalo-Universitaire OMICARE)

  • Christine Carapito

    (Infrastructure Nationale de Protéomique ProFI)

  • Dan Lipsker

    (Hôpitaux Universitaires de Strasbourg)

  • Kristine Schauer

    (CNRS
    Université Paris-Saclay)

  • Philippe Rondé

    (Université de Strasbourg
    Faculté de Pharmacie)

  • Vincent Hyenne

    (Tumor Biomechanics
    INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

  • Jacky G. Goetz

    (Tumor Biomechanics
    INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS))

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.

Suggested Citation

  • Katerina Jerabkova-Roda & Marina Peralta & Kuang-Jing Huang & Antoine Mousson & Clara Bourgeat Maudru & Louis Bochler & Ignacio Busnelli & Rabia Karali & Hélène Justiniano & Lucian-Mihai Lisii & Phili, 2025. "Peripheral positioning of lysosomes supports melanoma aggressiveness," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58528-5
    DOI: 10.1038/s41467-025-58528-5
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    References listed on IDEAS

    as
    1. Katerina Jerabkova-Roda & Marina Peralta & Kuang-Jing Huang & Antoine Mousson & Clara Bourgeat Maudru & Louis Bochler & Ignacio Busnelli & Rabia Karali & Hélène Justiniano & Lucian-Mihai Lisii & Phili, 2025. "Peripheral positioning of lysosomes supports melanoma aggressiveness," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    2. Samrat T. Kundu & Caitlin L. Grzeskowiak & Jared J. Fradette & Laura A. Gibson & Leticia B. Rodriguez & Chad J. Creighton & Kenneth L. Scott & Don L. Gibbons, 2018. "TMEM106B drives lung cancer metastasis by inducing TFEB-dependent lysosome synthesis and secretion of cathepsins," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    3. Larissa Heinrich & Davis Bennett & David Ackerman & Woohyun Park & John Bogovic & Nils Eckstein & Alyson Petruncio & Jody Clements & Song Pang & C. Shan Xu & Jan Funke & Wyatt Korff & Harald F. Hess &, 2021. "Whole-cell organelle segmentation in volume electron microscopy," Nature, Nature, vol. 599(7883), pages 141-146, November.
    4. Juliane Winkler & Abisola Abisoye-Ogunniyan & Kevin J. Metcalf & Zena Werb, 2020. "Concepts of extracellular matrix remodelling in tumour progression and metastasis," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
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    Cited by:

    1. Katerina Jerabkova-Roda & Marina Peralta & Kuang-Jing Huang & Antoine Mousson & Clara Bourgeat Maudru & Louis Bochler & Ignacio Busnelli & Rabia Karali & Hélène Justiniano & Lucian-Mihai Lisii & Phili, 2025. "Peripheral positioning of lysosomes supports melanoma aggressiveness," Nature Communications, Nature, vol. 16(1), pages 1-16, December.

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