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dc.contributor.authorRodriguez-Hernandez, Irene
dc.contributor.authorMaiques Carlos, Oscar
dc.contributor.authorKohlhammer, Leonie
dc.contributor.authorCantelli, Gaia
dc.contributor.authorPerdrix-Rosell, Anna
dc.contributor.authorMonger, Joanne
dc.contributor.authorFanshawe, Bruce
dc.contributor.authorBridgeman, Victoria L.
dc.contributor.authorKaragiannis, Sophia N.
dc.contributor.authorPenin, Rosa M.
dc.contributor.authorMarcolval, Joaquim
dc.contributor.authorMartí Laborda, Rosa Ma.
dc.contributor.authorMatias-Guiu, Xavier
dc.contributor.authorFruhwirth, Gilbert O.
dc.contributor.authorOrgaz, Jose L.
dc.contributor.authorMalanchi, Ilaria
dc.contributor.authorSanz Moreno, Victoria
dc.description.abstractMelanoma 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.
dc.description.sponsorshipThis work was supported by Cancer Research UK (CRUK) C33043/A12065 and C33043/A24478 (V.S.-M., I.R.-H., O.M., L.K., G.C. B.F. and J.L.O.); Royal Society RG110591 (V.S.-M.); Barts Charity (V.S.-M., I.R.-H., O.M., J.M. and J.L.O.); Fundacion Alfonso Martin Escudero and Marie Sklodowska-Curie Action, grant agreement No 659022 (I.R.-H.); MRC C97993H (G.C.); The Harry J. Lloyd Charitable Trust (J.L.O. and V.S.-M.); Francis Crick Institute core funding from CRUK FC001112, MRC FC001112 and the Wellcome Trust FC001112 (I.M. and A.P.); CRUK C48390/A21153, CRUK/EPSRC and Wellcome Trust/EPSRC WT 203148/Z/16/Z (G.O.F.); NIHR BRC at Guy’s and St Thomas’ NHS Foundation Trust and KCL IS-BRC-1215–20006, CRUK C30122/A11527 and C30122/A15774, MRC MR/L023091/1, CRUK/NIHR in England/DoH for Scotland, Wales and Northern Ireland ECMC C10355/A15587 (S.N.K.); ISCIII/FEDER “Una manera de hacer Europa” FIS-PI1500711 and PI18/00573 (R.M.M.); CIBERONC CB16/12/0023 (R.M.M and X.M.-G). Views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.
dc.publisherNature Research
dc.relation.isformatofReproducció del document publicat a:
dc.relation.ispartofNature Communications, 2020, vol. 11, núm. 1, p. 5315
dc.rightscc-by (c) Rodriguez-Hernandez, Irene et al., 2020
dc.titleWNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion

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cc-by (c) Rodriguez-Hernandez, Irene et al., 2020
Except where otherwise noted, this item's license is described as cc-by (c) Rodriguez-Hernandez, Irene et al., 2020