The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumors

Wang, Weigang; Mouneimne, Ghassan; Sidani, Mazen; Wyckoff, Jeffrey; Chen, Xiaoming; Makris, Anastasia; Goswami, Sumanta; Bresnick, Anne R.; Condeelis, John S.

doi:10.1083/jcb.200510115

Cited by 237 publications

(148 citation statements)

References 29 publications

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…Other studies have demonstrated that cofilin localizes to the lamellipodium tip immediately upon epidermal growth factor stimulation where it facilitates actin assembly by creating free barbed ends (55,57), and site-specific activation of cofilin in live cells leads to membrane protrusion at that site (56). These observations are consistent with the idea that localized filament severing promotes actin reorganization and assembly through treadmilling of actin filaments at the leading edge and point to the importance of spatially restricting cofilin activity.…”

Section: Identification Of a Major G␣ Q / Ca 2ϩ -Independent Par-2 Sisupporting

confidence: 78%

β-Arrestin-dependent Regulation of the Cofilin Pathway Downstream of Protease-activated Receptor-2

Zoudilova¹,

Kumar

et al. 2007

Journal of Biological Chemistry

132

133

View full text Add to dashboard Cite

␤-Arrestins are pleiotropic molecules that mediate signal desensitization, G-protein-independent signaling, scaffolding of signaling molecules, and chemotaxis. Protease-activated receptor-2 (PAR-2), a G␣ q/11 -coupled receptor, which has been proposed as a therapeutic target for inflammation and cancer, requires the scaffolding function of ␤-arrestins for chemotaxis. We hypothesized that PAR-2 can trigger specific responses by differential activation of two pathways, one through classic G␣ q /Ca 2؉ signaling and one through ␤-arrestins, and we proposed that the latter involves scaffolding of proteins involved in cell migration and actin assembly. Here we demonstrate the following.

show abstract

Section: Identification Of a Major G␣ Q / Ca 2ϩ -Independent Par-2 Sisupporting

confidence: 78%

β-Arrestin-dependent Regulation of the Cofilin Pathway Downstream of Protease-activated Receptor-2

Zoudilova¹,

Kumar

et al. 2007

Journal of Biological Chemistry

132

133

View full text Add to dashboard Cite

show abstract

“…Together with our observations, these results support the view that LIMK1 is required for the migration and invasion of various types of cancer cells. In contrast, other groups have reported that overexpression of LIMK1 decreases the motility and invasion of Rastransformed fibroblasts and mammary tumor cells (21,22). These seemingly contradictory results may be explained by differences in expression levels of ectopic LIMK1 or the different cell types used in these studies, in which the expression levels of endogenous LIMK1 or related genes, such as cofilin/ADF, LIMK2, TESKs (48), SSHs, Rho GTPases, or other actin regulators, may differ.…”

Section: Discussioncontrasting

confidence: 48%

Suppression of the Invasive Capacity of Rat Ascites Hepatoma Cells by Knockdown of Slingshot or LIM Kinase

Horita

Ohashi

Mukai

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…Cofilin activity at the leading edge is essential, but when uncontrolled can either inhibit protrusion formation or confer cells with metastatic potential (24,37,38). We observed that, in the absence of ␤-arrestins, cofilin localization to the leading edge and association with CIN is impaired, resulting in decreased generation of free actin barbed ends, defective membrane protrusion, and decreased cell migration.…”

Section: Discussionmentioning

confidence: 73%

β-Arrestins Scaffold Cofilin with Chronophin to Direct Localized Actin Filament Severing and Membrane Protrusions Downstream of Protease-activated Receptor-2

Zoudilova

Min

Richards

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Protease-activated receptor-2 (PAR-2) mediates pro-inflammatory signals in a number of organs, including enhancing leukocyte recruitment to sites of injury and infection. At the cellular level, PAR-2 promotes activation of the actin filamentsevering protein cofilin, which is crucial for the reorganization of the actin cytoskeleton and chemotaxis. These responses require the scaffolding functions of ␤-arrestins; however, the mechanism by which ␤-arrestins spatially regulate cofilin activity and the role of this pathway in primary cells has not been investigated. Here, using size-exclusion chromatography and co-immunoprecipitation, we demonstrate that PAR-2 promotes the formation of a complex containing ␤-arrestins, cofilin, and chronophin (CIN) in primary leukocytes and cultured cells. Both association of cofilin with CIN and cell migration are inhibited in leukocytes from ␤-arrestin-2 ؊/؊ mice. We show that, in response to PAR-2 activation, ␤-arrestins scaffold cofilin with its upstream activator CIN, to facilitate the localized generation of free actin barbed ends, leading to membrane protrusion. These studies suggest that a major role of ␤-arrestins in chemotaxis is to spatially regulate cofilin activity to facilitate the formation of a leading edge, and that this pathway may be important for PAR-2-stimulated immune cell migration.Protease-activated-receptor-2 (PAR-2) 2 is a G-protein-coupled receptor that signals, through ␤-arrestin-promoted scaffolds, to promote reorganization of the actin cytoskeleton and chemotaxis (1, 2). In vivo, PAR-2 plays an important role in the recruitment of leukocytes to the sites of inflammation, because this is impaired in PAR-2 Ϫ/Ϫ mice and enhanced by administration of PAR-2 agonists (3-8). However, no studies have yet linked ␤-arrestin-dependent scaffolding of actin assembly proteins to PAR-2-stimulated chemotaxis under physiological conditions.␤-Arrestins are multifunctional proteins that mediate receptor desensitization and internalization and serve as signaling scaffolds. A role for ␤-arrestin scaffolds in signaling by PAR-2 and other receptors was first identified for the spatial regulation of ERK1/2 activity (9 -11). They are now known to scaffold numerous other signaling molecules (12-15), many of which are involved in actin reorganization and chemotaxis (1, 13, 16 -19). An attractive hypothesis is that ␤-arrestins exert spatial control over actin assembly events at the leading edge to promote membrane protrusion and cell migration. A recent advance in this field was the discovery that ␤-arrestins are required for PAR-2-dependent activation of the actin filamentsevering protein, cofilin (14), which binds to the sides of actin filaments, destabilizing them and promoting their severing. Filament severing has two functions: the reorganization of existing filaments and the creation of free actin barbed ends for monomer addition (20). Actin is a polar molecule containing a barbed and pointed end; addition of actin monomers to a growing filament occurs at the barbed end. Alt...

show abstract

The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumors

Cited by 237 publications

References 29 publications

β-Arrestin-dependent Regulation of the Cofilin Pathway Downstream of Protease-activated Receptor-2

β-Arrestin-dependent Regulation of the Cofilin Pathway Downstream of Protease-activated Receptor-2

Suppression of the Invasive Capacity of Rat Ascites Hepatoma Cells by Knockdown of Slingshot or LIM Kinase

β-Arrestins Scaffold Cofilin with Chronophin to Direct Localized Actin Filament Severing and Membrane Protrusions Downstream of Protease-activated Receptor-2

Contact Info

Product

Resources

About