Actin-depolymerizing Factor and Cofilin-1 Play Overlapping Roles in Promoting Rapid F-Actin Depolymerization in Mammalian Nonmuscle Cells

Hotulainen, Pirta; Paunola, Eija; Vartiainen, Maria K.; Lappalainen, Pekka

doi:10.1091/mbc.e04-07-0555

Cited by 343 publications

(357 citation statements)

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“…NIH-PA Author Manuscript NIH-PA Author Manuscript polymerization and increase the rate of actin depolymerization (hence replenishing G-actin in the cell) 40,[44][45][46] . These studies have shown that nM concentrations of cofilin can sever actin filaments efficiently, thereby generating free actin filament barbed and pointed ends that are available for polymerization or depolymerization depending on the free G-actin concentration and the availability of barbed-end-capping proteins [44][45][46].…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…Unicellular organisms such as yeasts usually have only one ADF/cofilin-type protein, whereas multicellular organisms typically have several isoforms. In some cultured mammalian cell lines 40 and invasive mammary tumour cells 10,43 , cofilin 1 is the most abundant isoform, whereas ADF is expressed at much lower levels (5%). Therefore, for this Review 'cofilin' will refer to cofilin 1, the most abundant isoform found in invasive mammary tumour cells 10,12 .…”

Section: Biochemistry Of the Cofilin Pathwaymentioning

confidence: 99%

“…Second, the cell behaviour chosen for analysis is often different, resulting in apparently conflicting conclusions. For example, the inhibition of cofilin activity in mammalian cell lines with either small interfering RNA (siRNA) 40 or the expression of constitutively active LIMK domain 54 inhibits cell motility, but is reported to increase lamellipod size in Drosophila melanogaster S2 cells 55 . Expression of the wild-type or the nonphosphorylatable cofilin mutant S3A increases melanoma cell migration on vitronectin 56 , but S3A is reported to inhibit chemotaxis in mammary tumour cells 30 .…”

Section: Cell Biology Of the Cofilin Pathwaymentioning

confidence: 99%

“…All mammals are predicted to have a single ADF isoform expressed most strongly in epithelia and neurons, and two cofilin isoforms, a non-muscle type cofilin 1 expressed in most embryonic and adult cells, and a muscle-type cofilin 2 expressed almost exclusively in skeletal muscle 62 . Based on studies in various mouse cells, cofilin 1 is the predominant isoform in non-muscle cells, expressed at 6-11 times greater molar amounts than ADF 40 . Wang et al 10 has shown that the cofilin 1 isoform is selectively upregulated in invasive mammary tumour cells in rats.…”

Section: Boxmentioning

confidence: 99%

“…These types of cell protrusions are essential path-finding structures in chemotaxis, cell migration and invasion 38 . The cofilin pathway has emerged recently as a central player in the generation of free barbed ends 39 and actin filament-turnover 40 in various motile cells, including mammary carcinoma cells 38,39 , fibroblasts 40 , Dictyostelium discoideum 41 and glioblastoma cells 42 during the formation of these path-finding structures.…”

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The cofilin pathway in breast cancer invasion and metastasis

Wang¹,

2007

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Recent evidence indicates that metastatic capacity is an inherent feature of breast tumours and not a rare, late acquired event. This has led to new models of metastasis. The interpretation of expression-profiling data in the context of these new models has identified the cofilin pathway as a major determinant of metastasis. Recent studies indicate that the overall activity of the cofilin pathway, and not that of any single gene within the pathway, determines the invasive and metastatic phenotype of tumour cells. These results predict that inhibitors directed at the output of the cofilin pathway will have therapeutic benefit in combating metastasis.Tumour cell motility is the hallmark of invasion and an essential step in metastasis 1,2 . The identification of molecular pathways that contribute to tumour cell motility and invasion is essential for understanding how motility is initiated in tumour cells and how the tumour microenvironment contributes to cell migration. The identification of the molecular pathways of tumour cell invasion will provide new diagnostic approaches and targets for the treatment of metastatic cancer. Recent studies using new technologies, including highdensity microarray-based expression profiling, intravital imaging and the collection of invasive tumour cells from live tumours, have started to extend the traditional model of metastasis and supply new diagnostic and therapeutic markers of metastatic disease.According to the traditional model of metastasis, metastases result from a process similar to Darwinian evolution whereby natural selection works on individual tumour cells to select © 2007 Nature Publishing Group Correspondence to: J.C. Condeeli@aecom.yu.edu. Competing interests statementThe authors declare no competing financial interests. for stable genetic changes. The cells so selected are very rare, and the metastatic cells that arise from this progressive selection of stable genetic mutations within the primary tumour cause metastasis late in tumour progression 3 . However, studies of mammary tumours in mice [4][5][6][7] , expression profiling of both whole human breast tumours 8,9 and the invasive subpopulation of tumour cells isolated from rat and mouse mammary tumours [10][11][12] suggest that the metastatic ability of breast tumours is encoded throughout the bulk of the primary tumour, involves transient changes in gene expression and is acquired at much earlier stages of tumour progression than postulated by the traditional model. These results suggest that a Darwinian-like evolution is accompanied by, and may contribute to, microenvironmentinduced transient changes in gene expression that support the invasive and metastatic phenotype. These results have led to new models where the microenvironment initiates the expression of genes that induce cell motility, invasion and metastasis 11,13 . In the 'tumour microenvironment invasion model' it is proposed that oncogenic mutations in tumour cells lead to microenvironments that are potentially encoded throughout the b...

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Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Section: Biochemistry Of the Cofilin Pathwaymentioning

confidence: 99%

Section: Cell Biology Of the Cofilin Pathwaymentioning

confidence: 99%

Section: Boxmentioning

confidence: 99%

mentioning

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The cofilin pathway in breast cancer invasion and metastasis

Wang¹,

2007

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Cofilin promotes vasculogenic mimicry by regulating the actin cytoskeleton in human breast cancer cells

2023

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Vasculogenic mimicry (VM) is the formation of microvascular channels by cancer cells. VM requires cellular processes that are regulated by changes in cellular migration and morphology. Cofilin (CFL), a key regulator of actin depolymerization, has been reported to affect malignant phenotypes of cancer. We show that treatment with inhibitors of actin dynamics suppresses VM in MDA-MB-231 human breast cancer cells. We established CFL-knockout (KO) MDA-MB-231 cells and found that VM was attenuated in CFL-KO cells. Although the re-expression of wild-type CFL restored VM in CFL-KO cells, inactive phosphomimetic CFL failed to do so. Collectively, our results demonstrate that CFL is a critical regulator of VM and implicate CFL as a novel therapeutic target for breast cancer.

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Patterning of Fibroblast and Matrix Anisotropy within 3D Confinement is Driven by the Cytoskeleton

Serbo

Kuo

Lewis

et al. 2015

Adv Healthcare Materials

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Effects of 3D confinement on cellular growth and matrix assembly are important in tissue engineering, developmental biology, and regenerative medicine. Polydimethylsiloxane wells with varying anisotropy are microfabicated using soft‐lithography. Microcontact printing of bovine serum albumin is used to block cell adhesion to surfaces between wells. The orientations of fibroblast stress fibers, microtubules, and fibronectin fibrils are examined 1 day after cell seeding using laser scanning confocal microscopy, and anisotropy is quantified using a custom autocorrelation analysis. Actin, microtubules, and fibronectin exhibit higher anisotropy coefficients for cells grown in rectangular wells with aspect ratios of 1:4 and 1:8, as compared to those in wells with lower aspect ratios or in square wells. The effects of disabling individual cytoskeletal components on fibroblast responses to anisotropy are then tested by applying actin or microtubule polymerization inhibitors, Rho kinase inhibitor, or by siRNA‐mediated knockdown of AXL or cofilin‐1. Latrunculin A decreases cytoskeletal and matrix anisotropy, nocodazole ablates both, and Y27632 mutes cellular polarity while decreasing matrix anisotropy. AXL siRNA knockdown has little effect, as does siRNA knockdown of cofilin‐1. These data identify several specific cytoskeletal strategies as targets for the manipulation of anisotropy in 3D tissue constructs.

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Actin-depolymerizing Factor and Cofilin-1 Play Overlapping Roles in Promoting Rapid F-Actin Depolymerization in Mammalian Nonmuscle Cells

Cited by 343 publications

References 47 publications

The cofilin pathway in breast cancer invasion and metastasis

The cofilin pathway in breast cancer invasion and metastasis

Cofilin promotes vasculogenic mimicry by regulating the actin cytoskeleton in human breast cancer cells

Patterning of Fibroblast and Matrix Anisotropy within 3D Confinement is Driven by the Cytoskeleton

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