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WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion

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  • Irene Rodriguez-Hernandez

    (Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square
    Randall Division of Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London)

  • Oscar Maiques

    (Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square
    Randall Division of Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London)

  • Leonie Kohlhammer

    (Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square
    Randall Division of Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London)

  • Gaia Cantelli

    (Randall Division of Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London
    Duke University)

  • Anna Perdrix-Rosell

    (Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square
    Randall Division of Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London
    Tumour Host Interaction Laboratory, The Francis Crick Institute)

  • Joanne Monger

    (Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square)

  • Bruce Fanshawe

    (Randall Division of Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London
    School of Biomedical Engineering and Imaging Sciences, Kings’ College London)

  • Victoria L. Bridgeman

    (Tumour Host Interaction Laboratory, The Francis Crick Institute)

  • Sophia N. Karagiannis

    (St John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London and NIHR Biomedical Research Centre at Guy’s and St Thomas’ Hospitals and King’s College London)

  • Rosa M. Penin

    (Hospital Universitari de Bellvitge, IDIBELL, l’Hospitalet de Llobregat)

  • Joaquim Marcolval

    (Hospital Universitari de Bellvitge, IDIBELL, l’Hospitalet de Llobregat)

  • Rosa M. Marti

    (University of Lleida, IRB LleidaI, CIBERONC)

  • Xavier Matias-Guiu

    (University of Lleida, IRB Lleida, CIBERONC)

  • Gilbert O. Fruhwirth

    (School of Biomedical Engineering and Imaging Sciences, Kings’ College London)

  • Jose L. Orgaz

    (Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square
    Randall Division of Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London
    CSIC-UAM)

  • Ilaria Malanchi

    (Tumour Host Interaction Laboratory, The Francis Crick Institute)

  • Victoria Sanz-Moreno

    (Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square
    Randall Division of Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London)

Abstract

Melanoma is a highly aggressive tumour that can metastasize very early in disease progression. Notably, melanoma can disseminate using amoeboid invasive strategies. We show here that high Myosin II activity, high levels of ki-67 and high tumour-initiating abilities are characteristic of invasive amoeboid melanoma cells. Mechanistically, we find that WNT11-FZD7-DAAM1 activates Rho-ROCK1/2-Myosin II and plays a crucial role in regulating tumour-initiating potential, local invasion and distant metastasis formation. Importantly, amoeboid melanoma cells express both proliferative and invasive gene signatures. As such, invasive fronts of human and mouse melanomas are enriched in amoeboid cells that are also ki-67 positive. This pattern is further enhanced in metastatic lesions. We propose eradication of amoeboid melanoma cells after surgical removal as a therapeutic strategy.

Suggested Citation

  • Irene Rodriguez-Hernandez & Oscar Maiques & Leonie Kohlhammer & Gaia Cantelli & Anna Perdrix-Rosell & Joanne Monger & Bruce Fanshawe & Victoria L. Bridgeman & Sophia N. Karagiannis & Rosa M. Penin & J, 2020. "WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion," Nature Communications, Nature, vol. 11(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18951-2
    DOI: 10.1038/s41467-020-18951-2
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    Cited by:

    1. Eva Crosas-Molist & Vittoria Graziani & Oscar Maiques & Pahini Pandya & Joanne Monger & Remi Samain & Samantha L. George & Saba Malik & Jerrine Salise & Valle Morales & Adrien Le Guennec & R. Andrew A, 2023. "AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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