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

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 amo...

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Bibliographic Details
Published in:	Nature communications Vol. 11; no. 1; pp. 5315 - 20
Main Authors:	Rodriguez-Hernandez, Irene, Maiques, Oscar, Kohlhammer, Leonie, Cantelli, Gaia, Perdrix-Rosell, Anna, Monger, Joanne, Fanshawe, Bruce, Bridgeman, Victoria L., Karagiannis, Sophia N., Penin, Rosa M., Marcolval, Joaquim, Marti, Rosa M., Matias-Guiu, Xavier, Fruhwirth, Gilbert O., Orgaz, Jose L., Malanchi, Ilaria, Sanz-Moreno, Victoria
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 20-10-2020 Nature Publishing Group Nature Portfolio
Subjects:	13/1 13/105 13/106 13/51 13/89 13/95 14 14/19 38 38/77 631/67/1813/1634 631/67/71 631/80/86/2341 Animals Cell Transformation, Neoplastic Female Frizzled Receptors - genetics Frizzled Receptors - metabolism Humanities and Social Sciences Humans Male Melanoma Melanoma - genetics Melanoma - metabolism Melanoma - pathology Metastases Metastasis Mice Mice, SCID Microfilament Proteins - genetics Microfilament Proteins - metabolism multidisciplinary Myosin Myosin Type II - genetics Myosin Type II - metabolism Neoplasm Invasiveness rho GTP-Binding Proteins - genetics rho GTP-Binding Proteins - metabolism rho-Associated Kinases - genetics rho-Associated Kinases - metabolism Science Science (multidisciplinary) Signal Transduction Tumors Wnt Proteins - genetics Wnt Proteins - metabolism
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Summary:	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. Amoeboid cells are associated with melanoma invasive capacity. Here, the authors show that the WNT11-FZD7-DAAM1 pathway regulates tumour-initiating potential, invasion and metastasis lead by amoeboid cells in the invasive front of melanoma tumours.
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-020-18951-2