Differential roles of Rho-kinase and myosin light chain kinase in regulating shape, adhesion, and migration of HT1080 fibrosarcoma cells

Niggli, Verena; Schmid, Manuela; Nievergelt, Alexandra

doi:10.1016/j.bbrc.2006.03.022

Cited by 35 publications

(33 citation statements)

References 34 publications

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“…This augmentation of migration by blebbistatin treatment has been previously reported by us as well as by other groups. 13,[23][24][25] Importantly, the migration speed of GFP-Asef2 cells was significantly decreased compared with that observed with GFP cells, and blebbastatin treatment abolished this Asef2 effect on migration (Fig. 2D).…”

Section: Resultsmentioning

confidence: 81%

The Rho family GEF Asef2 regulates cell migration in three dimensional (3D) collagen matrices through myosin II

Jean

Yang

Majumdar

et al. 2014

Cell Adhesion & Migration

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Cell migration is fundamental to a variety of physiological processes, including tissue development, homeostasis, and regeneration. Migration has been extensively studied with cells on 2-dimensional (2D) substrates, but much less is known about cell migration in 3D environments. Tissues and organs are 3D, which is the native environment of cells in vivo, pointing to a need to understand migration and the mechanisms that regulate it in 3D environments. To investigate cell migration in 3D environments, we developed microfluidic devices that afford a controlled, reproducible platform for generating 3D matrices. Using these devices, we show that the Rho family guanine nucleotide exchange factor (GEF) Asef2 inhibits cell migration in 3D type I collagen (collagen I) matrices. Treatment of cells with the myosin II (MyoII) inhibitor blebbistatin abolished the decrease in migration by Asef2. Moreover, Asef2 enhanced MyoII activity as shown by increased phosphorylation of serine 19 (S19). Furthermore, Asef2 increased activation of Rac, which is a Rho family small GTPase, in 3D collagen I matrices. Inhibition of Rac activity by treatment with the Rac-specific inhibitor NSC23766 abrogated the Asef2-promoted increase in S19 MyoII phosphorylation. Thus, our results indicate that Asef2 regulates cell migration in 3D collagen I matrices through a Rac-MyoII-dependent mechanism.

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Section: Resultsmentioning

confidence: 81%

The Rho family GEF Asef2 regulates cell migration in three dimensional (3D) collagen matrices through myosin II

Jean

Yang

Majumdar

et al. 2014

Cell Adhesion & Migration

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“…Instead the ROCK related kinases, MRCKa and b function redundantly with ROCK1 and 2 to regulate actomyosin [47]. ROCK and MLCK have been shown to play distinct but complementary roles in the regulation of MLC phosphorylation, actin structures and motility of cells in 2D tissue culture conditions [107][108][109][110]. Elevated MLCK expression has been detected in numerous tumour types [111][112][113][114] and cancer cell lines [115][116][117] suggesting that increased MLCK activity resulting from overexpression or increased calcium transients might act to drive cancer cell motility in vivo, possibly in co-operation with ROCK.…”

Section: Actin Organisation In Complex Environmentsmentioning

confidence: 99%

The actin cytoskeleton in cancer cell motility

Olson

Sahai

2008

Clin Exp Metastasis

492

392

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Cancer cell metastasis is a multi-stage process involving invasion into surrounding tissue, intravasation, transit in the blood or lymph, extravasation, and growth at a new site. Many of these steps require cell motility, which is driven by cycles of actin polymerization, cell adhesion and acto-myosin contraction. These processes have been studied in cancer cells in vitro for many years, often with seemingly contradictory results. The challenge now is to understand how the multitude of in vitro observations relates to the movement of cancer cells in living tumour tissue. In this review we will concentrate on actin protrusion and acto-myosin contraction. We will begin by presenting some general principles summarizing the widely-accepted mechanisms for the co-ordinated regulation of actin polymerization and contraction. We will then discuss more recent studies that investigate how experimental manipulation of actin dynamics affects cancer cell invasion in complex environments and in vivo.

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“…Absence of MLCK Promotes SMC Migration-The prevalent view is that MLCK promotes cell retraction through actomyosin contraction and that the inhibition of MLCK will reduce migration velocity (16,34,43). To examine the migration behaviors after MLCK deletion, we first performed explant assays in culture, which resembled the tissue environment for cell migration (44).…”

Section: Characterization Of Mlck-deficientmentioning

confidence: 99%

“…MLCK regulates myosin II-mediated periodic lamellipodial contraction at the cell periphery (32). Because most proposed hypotheses are based on evidence from the application of nonspecific MLCK inhibitors (16,(33)(34)(35), the role of MLCK in cell migration remains controversial. For example, MLCK is activated at the leading edge, but myosin II is nearly non-existent in this area (36).…”

mentioning

confidence: 99%

Myosin Light Chain Kinase (MLCK) Regulates Cell Migration in a Myosin Regulatory Light Chain Phosphorylation-independent Mechanism

Chen

Tao

Wen

et al. 2014

Journal of Biological Chemistry

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Background: MLCK in cell migration remains controversial. Results: MLCK deletion causes enhanced cell protrusion along with a reduction of membrane tension and is rescued by kinase-dead MLCK or five-DFRXXL motif. Conclusion: MLCK regulates cell migration not by myosin regulatory light chain phosphorylation but possibly through a membrane tension-based mechanism. Significance: Our results shed light on a novel regulatory mechanism of protrusion during cell migration.

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Differential roles of Rho-kinase and myosin light chain kinase in regulating shape, adhesion, and migration of HT1080 fibrosarcoma cells

Cited by 35 publications

References 34 publications

The Rho family GEF Asef2 regulates cell migration in three dimensional (3D) collagen matrices through myosin II

The Rho family GEF Asef2 regulates cell migration in three dimensional (3D) collagen matrices through myosin II

The actin cytoskeleton in cancer cell motility

Myosin Light Chain Kinase (MLCK) Regulates Cell Migration in a Myosin Regulatory Light Chain Phosphorylation-independent Mechanism

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