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

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, Joaquim Marcolval, Rosa M. Marti, Xavier Matias-Guiu, Gilbert O. Fruhwirth, Jose L. Orgaz, Ilaria Malanchi and Victoria Sanz-Moreno ()
Additional contact information
Irene Rodriguez-Hernandez: Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square
Oscar Maiques: Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square
Leonie Kohlhammer: Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square
Gaia Cantelli: Randall Division of Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London
Anna Perdrix-Rosell: Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square
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
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
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

Nature Communications, 2020, vol. 11, issue 1, 1-20

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18951-2

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