Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens

Ivković, Sanja; Beadle, Christopher D.; Noticewala, Sonal S.; Massey, Susan Christine; Swanson, Kristin R.; Toro, Laura Norwood; Bresnick, Anne R.; Canoll, Peter; Rosenfeld, Steven S.

doi:10.1091/mbc.e11-01-0039

Cited by 89 publications

(77 citation statements)

References 50 publications

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“…Myosin II is a key protein required for elongating the cells and allowing them to move through tight spaces. Recently, it was demonstrated that blebbistatin could significantly reduce glioma cell migration in in vitro experiments as well as in ex vivo brain slices even in the presence of multiple motogens such as the growth factors EGF and/or PDGF [192]. These results are promising, but further studies need to be done to demonstrate effectiveness in humans.…”

Section: Resultsmentioning

confidence: 99%

The biology and mathematical modelling of glioma invasion: a review

Alfonso

Talkenberger

Seifert

et al. 2017

J. R. Soc. Interface.

187

163

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Adult gliomas are aggressive brain tumours associated with low patient survival rates and limited life expectancy. The most important hallmark of this type of tumour is its invasive behaviour, characterized by a markedly phenotypic plasticity, infiltrative tumour morphologies and the ability of malignant progression from low-to high-grade tumour types. Indeed, the widespread infiltration of healthy brain tissue by glioma cells is largely responsible for poor prognosis and the difficulty of finding curative therapies. Meanwhile, mathematical models have been established to analyse potential mechanisms of glioma invasion. In this review, we start with a brief introduction to current biological knowledge about glioma invasion, and then critically review and highlight future challenges for mathematical models of glioma invasion.

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Section: Resultsmentioning

confidence: 99%

The biology and mathematical modelling of glioma invasion: a review

Alfonso

Talkenberger

Seifert

et al. 2017

J. R. Soc. Interface.

187

163

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“…1G; supplementary material Fig. S3F; Hopkins et al, 2007;Ivkovic et al, 2012). However, there are other studies that report that myosin inhibition either does not decrease or actually increases cell migration speed (Kuo et al, 2011).…”

Section: Roles Of Actomyosin Contraction In Adhesion Dynamics and Celmentioning

confidence: 98%

Displacement of p130Cas from focal adhesions links actomyosin contraction to cell migration

Machiyama

Harai

Loh

et al. 2014

Journal of Cell Science

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BSTRACTCell adhesion complexes provide platforms where cell-generated forces are transmitted to the extracellular matrix (ECM). Tyrosine phosphorylation of focal adhesion proteins is crucial for cells to communicate with the extracellular environment. However, the mechanisms that transmit actin cytoskeletal motion to the extracellular environment to drive cell migration are poorly understood. We find that the movement of p130Cas (Cas, also known as BCAR1), a mechanosensor at focal adhesions, correlates with actin retrograde flow and depends upon actomyosin contraction and phosphorylation of the Cas substrate domain (CasSD). This indicates that CasSD phosphorylation underpins the physical link between Cas and the actin cytoskeleton. Fluorescence recovery after photobleaching (FRAP) experiments reveal that CasSD phosphorylation, as opposed to the association of Cas with Src, facilitates Cas displacement from adhesion complexes in migrating cells. Furthermore, the stabilization of Src-Cas binding and inhibition of myosin II, both of which sustain CasSD phosphorylation but mitigate Cas displacement from adhesion sites, retard cell migration. These results indicate that Cas promotes cell migration by linking actomyosin contractions to the adhesion complexes through a dynamic interaction with Src as well as through the phosphorylation-dependent association with the actin cytoskeleton.

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“…Cancer metastasis is an equally complex process that depends on factors including the remodeling of the ECM and the capacity of the nucleus to deform (Harada et al, 2014;Wolf et al, 2013). Other work has shown that the ability of myosin-II to deform the nucleus can be a decisive factor in limiting glioma migration into brain tissue (Beadle et al, 2008;Ivkovic et al, 2012), but cancer cells in general show no universal lamina phenotype (reviewed in Foster et al, 2010). Although low levels of A-type lamin have been correlated with increased reoccurrence of colon cancers (Belt et al, 2011), A-type lamin was also found to be upregulated in certain skin and ovarian cancers (Hudson et al, 2007;Tilli et al, 2003), and higher expression of these lamin proteins has been associated with better clinical outcomes in breast cancer (Wazir et al, 2013).…”

Section: Mechanotransduction To the Nucleus -Downstream Of Ecm And Laminmentioning

confidence: 99%

The nuclear lamina is mechano-responsive to ECM elasticity in mature tissue

Swift

Discher

2014

Journal of Cell Science

187

165

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How cells respond to physical cues in order to meet and withstand the physical demands of their immediate surroundings has been of great interest for many years, with current research efforts focused on mechanisms that transduce signals into gene expression. Pathways that mechano-regulate the entry of transcription factors into the cell nucleus are emerging, and our most recent studies show that the mechanical properties of the nucleus itself are actively controlled in response to the elasticity of the extracellular matrix (ECM) in both mature and developing tissue. In this Commentary, we review the mechano-responsive properties of nuclei as determined by the intermediate filament lamin proteins that line the inside of the nuclear envelope and that also impact upon transcription factor entry and broader epigenetic mechanisms. We summarize the signaling pathways that regulate lamin levels and cell-fate decisions in response to a combination of ECM mechanics and molecular cues. We will also discuss recent work that highlights the importance of nuclear mechanics in niche anchorage and cell motility during development, hematopoietic differentiation and cancer metastasis, as well as emphasizing a role for nuclear mechanics in protecting chromatin from stress-induced damage.

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Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens

Cited by 89 publications

References 50 publications

The biology and mathematical modelling of glioma invasion: a review

The biology and mathematical modelling of glioma invasion: a review

Displacement of p130Cas from focal adhesions links actomyosin contraction to cell migration

The nuclear lamina is mechano-responsive to ECM elasticity in mature tissue

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