TY - JOUR
T1 - WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion
AU - Rodriguez-Hernandez, Irene
AU - Maiques, Oscar
AU - Kohlhammer, Leonie
AU - Cantelli, Gaia
AU - Perdrix-Rosell, Anna
AU - Monger, Joanne
AU - Fanshawe, Bruce
AU - Bridgeman, Victoria L
AU - Karagiannis, Sophia N
AU - Penin, Rosa M
AU - Marcolval, Joaquim
AU - Marti, Rosa M
AU - Matias-Guiu, Xavier
AU - Fruhwirth, Gilbert O
AU - Orgaz, Jose L
AU - Malanchi, Ilaria
AU - Sanz-Moreno, Victoria
N1 - Funding Information:
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). Views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85093079960&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-18951-2
DO - 10.1038/s41467-020-18951-2
M3 - Article
C2 - 33082334
SN - 2041-1723
VL - 11
SP - 5315
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5315
ER -
