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Regional activation of Myosin II in cancer cells drives tumor progression via a secretory cross-talk with the immune microenvironment

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journal contribution
posted on 16.12.2019 by Mirella Georgouli, Cecilia Herraiz, Eva Crosas-Molist, Bruce Fanshawe, Oscar Maiques, Anna Perdrix, Pahini Pandya, Irene Rodriguez-Hernandez, Kristina M Ilieva, Gaia Cantelli, Panagiotis Karagiannis, Silvia Mele, Hoyin Lam, Debra H Josephs, Xavier Matias-Guiu, Rosa M Marti, Frank O Nestle, Jose L Orgaz, Ilaria Malanchi, Gilbert O Fruhwirth, Sophia N Karagiannis, Victoria Sanz-Moreno
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-1α secretion and NF-κB 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.