Mechanical Cues Affect Migration and Invasion of Cells From Three Different Directions

Mierke, Claudia Tanja

doi:10.3389/fcell.2020.583226

Cited by 46 publications

(31 citation statements)

References 397 publications

(504 reference statements)

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“…Increased Myosin activation and consequently, increased stiffness are a common phenotype observed in cancer cells and their substrate ( Tse et al, 2012 ; Aguilar-Cuenca et al, 2014 ; van Helvert and Friedl, 2016 ; Ren et al, 2021 ). Increased substrate stiffness promotes migration in a wide range of cancers, suggesting increased Myosin activity can lead to increased cancer metastasis ( Aguilar-Cuenca et al, 2014 ; Emon et al, 2018 ; Mierke, 2020 ; Ren et al, 2021 ). Additionally, Fascin is highly expressed in many types of cancers, notably carcinomas ( Hashimoto et al, 2011 ; Ma and Machesky, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration

Lamb

Kaluarachchi

Lansakara

et al. 2021

eLife

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A key regulator of collective cell migrations, which drive development and cancer metastasis, is substrate stiffness. Increased substrate stiffness promotes migration and is controlled by Myosin. Using Drosophila border cell migration as a model of collective cell migration, we identify, for the first time, that the actin bundling protein Fascin limits Myosin activity in vivo. Loss of Fascin results in: increased activated Myosin on the border cells and their substrate, the nurse cells; decreased border cell Myosin dynamics; and increased nurse cell stiffness as measured by atomic force microscopy. Reducing Myosin restores on-time border cell migration in fascin mutant follicles. Further, Fascin’s actin bundling activity is required to limit Myosin activation. Surprisingly, we find that Fascin regulates Myosin activity in the border cells to control nurse cell stiffness to promote migration. Thus, these data shift the paradigm from a substrate stiffness-centric model of regulating migration, to uncover that collectively migrating cells play a critical role in controlling the mechanical properties of their substrate in order to promote their own migration. This understudied means of mechanical regulation of migration is likely conserved across contexts and organisms, as Fascin and Myosin are common regulators of cell migration.

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Section: Discussionmentioning

confidence: 99%

Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration

Lamb

Kaluarachchi

Lansakara

et al. 2021

eLife

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show abstract

“…Increased Myosin activation and consequently, increased stiffness are a common phenotype observed in cancer cells and their substrate (Aguilar-Cuenca et al, 2014;Ren et al, 2021;Tse et al, 2012;van Helvert and Friedl, 2016). Increased substrate stiffness promotes migration in a wide range of cancers, suggesting increased Myosin activity can lead to increased cancer metastasis (Aguilar-Cuenca et al, 2014;Emon et al, 2018;Mierke, 2020;Ren et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Fascin limits Myosin activity withinDrosophilaborder cells to control substrate stiffness and promote migration

Lamb

Kaluarachchi

Lansakara

et al. 2021

Preprint

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A key regulator of collective cell migrations, which drive development and cancer metastasis, is substrate stiffness. Increased substrate stiffness promotes migration and is controlled by Myosin. Using Drosophila border cell migration as a model of collective cell migration, we identify, for the first time, that the actin bundling protein Fascin limits Myosin activity in vivo. Loss of Fascin results in: increased activated Myosin on the border cells and their substrate, the nurse cells; decreased border cell Myosin dynamics; and increased nurse cell stiffness as measured by atomic force microscopy. Reducing Myosin restores on-time border cell migration in fascin mutant follicles. Further, Fascin’s actin bundling activity is required to limit Myosin activation. Surprisingly, we find that Fascin regulates Myosin activity in the border cells to control nurse cell stiffness to promote migration. Thus, these data shift the paradigm from a substrate stiffness-centric model of regulating migration, to uncover that collectively migrating cells play a critical role in controlling the mechanical properties of their substrate in order to promote their own migration. This new means of mechanical regulation of migration is likely conserved across contexts and organisms, as Fascin and Myosin are common regulators of cell migration.

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“…The development of technologies to assess cellular elasticity, such as AFM and micropipette aspiration, indicates that elasticity and motility of cancer cells are mutually correlated, and elasticity has been acknowledged as a biomarker for the invasive potency of cancer cells ( Wagh et al, 2008 ; Krause and Wolf, 2015 ). The relationship between cell elasticity and metastatic capacity has been established; however, several reports contradict one another ( Kwon et al, 2020 ; Mierke, 2014 ; Mierke, 2019 ; Mierke, 2020 ). For instance, highly metastatic ovarian HEY A8 cancer cells are softer than non-malignant ovarian epithelial cells, and the migratory potential of HEY A8 is coupled to the restructuring of the actin cytoskeleton ( Xu et al, 2020 ).…”

Section: Coupling Between Viscoelasticity and Cellular Motilitymentioning

confidence: 99%

Viscoelasticity, Like Forces, Plays a Role in Mechanotransduction

Mierke

2022

Front. Cell Dev. Biol.

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Viscoelasticity and its alteration in time and space has turned out to act as a key element in fundamental biological processes in living systems, such as morphogenesis and motility. Based on experimental and theoretical findings it can be proposed that viscoelasticity of cells, spheroids and tissues seems to be a collective characteristic that demands macromolecular, intracellular component and intercellular interactions. A major challenge is to couple the alterations in the macroscopic structural or material characteristics of cells, spheroids and tissues, such as cell and tissue phase transitions, to the microscopic interferences of their elements. Therefore, the biophysical technologies need to be improved, advanced and connected to classical biological assays. In this review, the viscoelastic nature of cytoskeletal, extracellular and cellular networks is presented and discussed. Viscoelasticity is conceptualized as a major contributor to cell migration and invasion and it is discussed whether it can serve as a biomarker for the cells’ migratory capacity in several biological contexts. It can be hypothesized that the statistical mechanics of intra- and extracellular networks may be applied in the future as a powerful tool to explore quantitatively the biomechanical foundation of viscoelasticity over a broad range of time and length scales. Finally, the importance of the cellular viscoelasticity is illustrated in identifying and characterizing multiple disorders, such as cancer, tissue injuries, acute or chronic inflammations or fibrotic diseases.

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Mechanical Cues Affect Migration and Invasion of Cells From Three Different Directions

Cited by 46 publications

References 397 publications

Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration

Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration

Fascin limits Myosin activity withinDrosophilaborder cells to control substrate stiffness and promote migration

Viscoelasticity, Like Forces, Plays a Role in Mechanotransduction

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