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      Modes of invasion during tumour dissemination

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          Abstract

          Cancer cell migration and invasion underlie metastatic dissemination, one of the major problems in cancer. Tumour cells exhibit a striking variety of invasion strategies. Importantly, cancer cells can switch between invasion modes in order to cope with challenging environments. This ability to switch migratory modes or plasticity highlights the challenges behind antimetastasis therapy design. In this Review, we present current knowledge on different tumour invasion strategies, the determinants controlling plasticity and arising therapeutic opportunities. We propose that targeting master regulators controlling plasticity is needed to hinder tumour dissemination and metastasis.

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          Most cited references144

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          Epithelial-mesenchymal transitions in development and disease.

          The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and in the differentiation of multiple tissues and organs. EMT also contributes to tissue repair, but it can adversely cause organ fibrosis and promote carcinoma progression through a variety of mechanisms. EMT endows cells with migratory and invasive properties, induces stem cell properties, prevents apoptosis and senescence, and contributes to immunosuppression. Thus, the mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
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            Non-muscle myosin II takes centre stage in cell adhesion and migration.

            Non-muscle myosin II (NM II) is an actin-binding protein that has actin cross-linking and contractile properties and is regulated by the phosphorylation of its light and heavy chains. The three mammalian NM II isoforms have both overlapping and unique properties. Owing to its position downstream of convergent signalling pathways, NM II is central in the control of cell adhesion, cell migration and tissue architecture. Recent insight into the role of NM II in these processes has been gained from loss-of-function and mutant approaches, methods that quantitatively measure actin and adhesion dynamics and the discovery of NM II mutations that cause monogenic diseases.
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              Plasticity of cell migration: a multiscale tuning model

              Cell migration underlies tissue formation, maintenance, and regeneration as well as pathological conditions such as cancer invasion. Structural and molecular determinants of both tissue environment and cell behavior define whether cells migrate individually (through amoeboid or mesenchymal modes) or collectively. Using a multiparameter tuning model, we describe how dimension, density, stiffness, and orientation of the extracellular matrix together with cell determinants—including cell–cell and cell–matrix adhesion, cytoskeletal polarity and stiffness, and pericellular proteolysis—interdependently control migration mode and efficiency. Motile cells integrate variable inputs to adjust interactions among themselves and with the matrix to dictate the migration mode. The tuning model provides a matrix of parameters that control cell movement as an adaptive and interconvertible process with relevance to different physiological and pathological contexts.
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                Author and article information

                Contributors
                victoria.sanz_moreno@kcl.ac.uk
                Journal
                Mol Oncol
                Mol Oncol
                10.1002/(ISSN)1878-0261
                MOL2
                Molecular Oncology
                John Wiley and Sons Inc. (Hoboken )
                1574-7891
                1878-0261
                09 December 2016
                January 2017
                : 11
                : 1 , Cancer metastasis ( doiID: 10.1002/mol2.2017.11.issue-1 )
                : 5-27
                Affiliations
                [ 1 ] Tumour Plasticity Team Randall Division of Cell and Molecular Biophysics King's College London UK
                Author notes
                [*] [* ] Correspondence

                V. Sanz‐Moreno, Tumour Plasticity Team, Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK

                E‐mail: victoria.sanz_moreno@ 123456kcl.ac.uk

                [†]

                Equal contribution

                Article
                MOL212019
                10.1002/1878-0261.12019
                5423224
                28085224
                d022c4fb-dff4-41ae-a6e0-b082822f5244
                © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 July 2016
                : 24 October 2016
                : 28 October 2016
                Page count
                Figures: 4, Tables: 0, Pages: 23, Words: 14800
                Funding
                Funded by: CRUK
                Award ID: C33043/A12065
                Funded by: Royal Society
                Award ID: RG110591
                Funded by: King's Overseas Scholarship
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                mol212019
                January 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.4 mode:remove_FC converted:25.07.2017

                Oncology & Radiotherapy
                actomyosin contractility,cancer metastasis,invasion,plasticity,rho gtpases
                Oncology & Radiotherapy
                actomyosin contractility, cancer metastasis, invasion, plasticity, rho gtpases

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