Regional Activation of Myosin II in Cancer Cells Drives Tumor Progression via a Secretory Cross-Talk with the Immune Microenvironment

Marigoula 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

doi:10.1016/j.cell.2018.12.038

Regional Activation of Myosin II in Cancer Cells Drives Tumor Progression via a Secretory Cross-Talk with the Immune Microenvironment

Marigoula 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. FruhwirthSophia N. Karagiannis, Victoria Sanz-Moreno

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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-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.

Original language	English
Pages (from-to)	757-774.e23
Number of pages	33
Journal	Cell
Volume	176
Issue number	4
Early online date	31 Jan 2019
DOIs	https://doi.org/10.1016/j.cell.2018.12.038
Publication status	Published - 7 Feb 2019

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Regional Activation of Myosin II_GEORGOULI_Accepted21Dec2018_GOLD VoRFinal published version, 10.9 MBLicence: CC BY

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Georgouli, M., Herraiz, C., Crosas-Molist, E., Fanshawe, B., Maiques, O., Perdrix, A., Pandya, P., Rodriguez-Hernandez, I., Ilieva, K. M., Cantelli, G., Karagiannis, P., Mele, S., Lam, H., Josephs, D. H., Matias-Guiu, X., Marti, R. M., Nestle, F. O., Orgaz, J. L., Malanchi, I., ... Sanz-Moreno, V. (2019). Regional Activation of Myosin II in Cancer Cells Drives Tumor Progression via a Secretory Cross-Talk with the Immune Microenvironment. Cell, 176(4), 757-774.e23. https://doi.org/10.1016/j.cell.2018.12.038

@article{2246c88c93e24ec1af1948af6a914c57,

title = "Regional Activation of Myosin II in Cancer Cells Drives Tumor Progression via a Secretory Cross-Talk with the Immune Microenvironment",

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-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.",

author = "Marigoula Georgouli and Cecilia Herraiz and Eva Crosas-Molist and Bruce Fanshawe and Oscar Maiques and Anna Perdrix and Pahini Pandya and Irene Rodriguez-Hernandez and Ilieva, {Kristina M.} and Gaia Cantelli and Panagiotis Karagiannis and Silvia Mele and Hoyin Lam and Josephs, {Debra H.} and Xavier Matias-Guiu and Marti, {Rosa M.} and Nestle, {Frank O.} and Orgaz, {Jose L.} and Ilaria Malanchi and Fruhwirth, {Gilbert O.} and Karagiannis, {Sophia N.} and Victoria Sanz-Moreno",

year = "2019",

month = feb,

day = "7",

doi = "10.1016/j.cell.2018.12.038",

language = "English",

volume = "176",

pages = "757--774.e23",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "4",

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Georgouli, M, Herraiz, C, Crosas-Molist, E , Fanshawe, B , Maiques, O , Perdrix, A , Pandya, P , Rodriguez-Hernandez, I , Ilieva, KM , Cantelli, G , Karagiannis, P , Mele, S , Lam, H , Josephs, DH, Matias-Guiu, X, Marti, RM, Nestle, FO , Orgaz, JL, Malanchi, I, Fruhwirth, GO, Karagiannis, SN & Sanz-Moreno, V 2019, 'Regional Activation of Myosin II in Cancer Cells Drives Tumor Progression via a Secretory Cross-Talk with the Immune Microenvironment', Cell, vol. 176, no. 4, pp. 757-774.e23. https://doi.org/10.1016/j.cell.2018.12.038

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 -

Regional Activation of Myosin II in Cancer Cells Drives Tumor Progression via a Secretory Cross-Talk with the Immune Microenvironment

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