Journal
CELL
Volume 176, Issue 4, Pages 757-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2018.12.038
Keywords
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Categories
Funding
- Cancer Research UK (CRUK) [C33043/A12065, C33043/A24478]
- Royal Society [RG110591]
- Harry J. Lloyd Charitable Trust
- Barts Charity
- NIHR Biomedical Research Centre
- Fundacion Alfonso Martin Escudero
- Fundacion Ramon Areces
- NIHR BRC at Guy's and St Thomas' NHS Foundation Trust and King's College London [IS-BRC-1215-20006]
- Breast Cancer Now [147]
- CRUK [C48390/A21153, C30122/A11527, C30122/A15774, FC001112]
- Medical Research Council (MRC) [MR/L023091/1]
- Academy of Medical Sciences
- CR UK/NIHR in England/DoH for Scotland, Wales and Northern Ireland Experimental Cancer Medicine Centre [C10355/A15587]
- MRC [FC001112]
- Wellcome Trust [FC001112]
- Worldwide Cancer Research [16-1135]
- FIS [PI12/00260, PI15/00711]
- Xarxa Catalana de Bancs de Tumours
- Tumour Banc Platform of RTICC [PT13/0010/0014]
- FMTV-3 [201331-31]
- Marie Sklodowska-Curie Action [H2020-MSCA-IF-2014-EF-ST]
- MRC [MR/L023091/1] Funding Source: UKRI
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ROCK-Myosin II drives fast rounded-amoeboid migration in cancer cells during metastatic dissemination. Analysis of human melanoma biopsies revealed that amoeboid melanoma cells with high Myosin II activity are predominant in the invasive fronts of primary tumors in proximity to CD206(+)CD163(+) tumor-associated macrophages and vessels. Proteomic analysis shows that ROCK Myosin II activity in amoeboid cancer cells controls an immunomodulatory secretome, enabling the recruitment of monocytes and their differentiation into tumor-promoting macrophages. Both amoeboid cancer cells and their associated macrophages support an abnormal vasculature, which ultimately facilitates tumor progression. Mechanistically, amoeboid cancer cells perpetuate their behavior via ROCK-Myosin II-driven IL-alpha secretion and NF-kappa B activation. Using an array of tumor models, we show that high Myosin II activity in tumor cells reprograms the innate immune microenvironment to support tumor growth. We describe an unexpected role for Myosin II dynamics in cancer cells controlling myeloid function via secreted factors.
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