TY - JOUR
T1 - Regional Activation of Myosin II in Cancer Cells Drives Tumor Progression via a Secretory Cross-Talk with the Immune Microenvironment
AU - Georgouli, Marigoula
AU - Herraiz, Cecilia
AU - Crosas-Molist, Eva
AU - Fanshawe, Bruce
AU - Maiques, Oscar
AU - Perdrix, Anna
AU - Pandya, Pahini
AU - Rodriguez-Hernandez, Irene
AU - Ilieva, Kristina M.
AU - Cantelli, Gaia
AU - Karagiannis, Panagiotis
AU - Mele, Silvia
AU - Lam, Hoyin
AU - Josephs, Debra H.
AU - Matias-Guiu, Xavier
AU - Marti, Rosa M.
AU - Nestle, Frank O.
AU - Orgaz, Jose L.
AU - Malanchi, Ilaria
AU - Fruhwirth, Gilbert O.
AU - Karagiannis, Sophia N.
AU - Sanz-Moreno, Victoria
PY - 2019/2/7
Y1 - 2019/2/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85061010359&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2018.12.038
DO - 10.1016/j.cell.2018.12.038
M3 - Article
C2 - 30712866
SN - 0092-8674
VL - 176
SP - 757-774.e23
JO - Cell
JF - Cell
IS - 4
ER -
