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Title: Regional Activation of Myosin II in Cancer Cells Drives Tumor Progression via a Secretory Cross-Talk with the Immune Microenvironment
Author: Georgouli, Mirella
Herraiz, Cecilia
Crosas Molist, Eva
Fanshawe, Bruce
Maiques, Oscar
Perdrix, Anna
Pandya, Pahini
Rodríguez Hernández, Irene
Ilieva, Kristina M.
Cantelli, Gaia
Karagiannis, Panagiotis
Mele, Silvia
Lam, Hoyin
Josephs, Debra H.
Matías Guiu, Xavier
Marti, Rosa M.
Nestle, Frank O.
Orgaz, Jose L.
Malanchi, Ilaria
Fruhwirth, Gilbert O.
Karagiannis, Sophia N.
Sanz Moreno, Victoria
Keywords: Càncer
Issue Date: 7-Feb-2019
Publisher: Cell Press
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Cell, 2019-02-07, Vol. 176, Issue 4, P. 757-774
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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