La señalización WNT11-FZD7-DAAM1 es compatible con las capacidades de iniciación de tumores y la invasión ameboide del melanoma
| Autor: | Joaquim Marcolval, Irene Rodriguez-Hernandez, Ilaria Malanchi, Gilbert O. Fruhwirth, Bruce Fanshawe, Leonie Kohlhammer, Rosa M. Martí, Oscar Maiques, R.M. Penín, Victoria L. Bridgeman, Joanne Monger, Xavier Matias-Guiu, Gaia Cantelli, Anna Perdrix-Rosell, Victoria Sanz-Moreno, Sophia N. Karagiannis, Jose L. Orgaz |
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| Přispěvatelé: | Cancer Research UK, Royal Society (UK), European Commission, Helmsley Charitable Trust, Wellcome Trust, NHS Foundation Trust, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Cáncer (España) |
| Rok vydání: | 2020 |
| Předmět: |
Male
rho GTP-Binding Proteins 0301 basic medicine Metastatic lesions General Physics and Astronomy WNT11-FZD7-DAAM Mice SCID Metastasis Mice RHO signalling 0302 clinical medicine Myosin lcsh:Science Càncer Melanoma Therapeutic strategy rho-Associated Kinases DAAM1 Multidisciplinary Cancer stem cells ki-67 Microfilament Proteins Rho-ROCK1 / 2-Myosin II 3. Good health Cell Transformation Neoplastic Signalling 030220 oncology & carcinogenesis Female Signal transduction metástasis Signal Transduction Medicina Science Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Metàstasi Cancer stem cell medicine melanoma Animals Humans Neoplasm Invasiveness Myosin Type II General Chemistry medicine.disease Frizzled Receptors Wnt Proteins 030104 developmental biology melanoma ameboide Cancer research lcsh:Q |
| Zdroj: | Biblos-e Archivo. Repositorio Institucional de la UAM Consejo Superior de Investigaciones Científicas (CSIC) Recercat. Dipósit de la Recerca de Catalunya instname Nature Communications, Vol 11, Iss 1, Pp 1-20 (2020) Biblos-e Archivo: Repositorio Institucional de la UAM Universidad Autónoma de Madrid Repositorio Abierto de la UdL Universitad de Lleida Rodriguez-Hernandez, I, Maiques, O, Kohlhammer, L, Cantelli, G, Perdrix-Rosell, A, Monger, J, Fanshawe, B, Bridgeman, V L, Karagiannis, S N, Penin, R M, Marcolval, J, Marti, R M, Matias-Guiu, X, Fruhwirth, G O, Orgaz, J L, Malanchi, I & Sanz-Moreno, V 2020, ' WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion ', Nature Communications, vol. 11, no. 1, 5315, pp. 5315 . https://doi.org/10.1038/s41467-020-18951-2 Digital.CSIC. Repositorio Institucional del CSIC Dipòsit Digital de la UB Universidad de Barcelona Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) Nature Communications |
| DOI: | 10.1038/s41467-020-18951-2 |
| Popis: | 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. This 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). |
| Databáze: | OpenAIRE |
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