Intermediate filament protein synemin contributes to the migratory properties of astrocytoma cells by influencing the dynamics of the actin cytoskeleton

Pan, Yihang; Jing, Runfeng; Pitre, Aaron; Williams, B. Jill; Skalli, Omar

doi:10.1096/fj.08-106187

Cited by 42 publications

(40 citation statements)

References 43 publications

(71 reference statements)

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“…Cytoskeletal reorganization of the actin filament is of central importance for cell motility and is essential for most types of cell migration. 36 Interestingly, synemin, a large IF protein structurally-similar to nestin, directly regulates F-actin and alpha-actinin in astrocytoma cells, 7,8 and is localized at their leading edge, which is essential for cell migration. 37 Conceivably, nestin may have a similar role in relation to actin in pancreatic cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Nestin is a novel target for suppressing pancreatic cancer cell migration, invasion and metastasis

Matsuda

Naito

Kawahara

et al. 2011

Cancer Biology & Therapy

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Nestin, is a class VI intermediate filament (IF) that is expressed in 30% of pancreatic ductal adenocarcinoma (pDaC) cases, and its expression in pDaC positively correlates with peripancreatic invasion. an expression vector carrying a short hairpin RNa (shRNa) targeting nestin was stably transfected into paNC-1 and pK-45h human pancreatic cancer cells, which express high nestin levels. alterations in morphology and alignment of actin filaments and α-tubulin were examined by phase-contrast and immunocytochemistry. effects on cell growth, migration in scratch and Boyden chamber assays, invasion, cell adhesion, and in vivo growth were determined. Differences in mRNa levels were examined by arrays. Nestin shRNa-transfected cells exhibited decreased nestin expression, a sheet-like appearance with tight cellcell adhesion, increased expression of filamentous F-actin and e-cadherin, and attenuated migration and invasion, both of which were enhanced following nestin re-expression. expression of α-tubulin, and in vitro cell growth and adhesion were not altered by nestin downregulation, whereas hepatic metastases were decreased. Thus, nestin plays important roles in pancreatic cancer cell migration, invasion and metastasis by selectively modulating the expression of actin and cell adhesion molecules, and may therefore be a novel therapeutic target in pDaC.

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Section: Discussionmentioning

confidence: 99%

Nestin is a novel target for suppressing pancreatic cancer cell migration, invasion and metastasis

Matsuda

Naito

Kawahara

et al. 2011

Cancer Biology & Therapy

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“…Furthermore, the cytoskeletal reorganization of the actin filament is important in cell motility and is essential for most types of cell migration (31). Previous studies have shown that synemin, one of the large IF proteins structurally similar to nestin, directly regulates F-actin and α-actinin in glioma cells (32,33). Nestin is also reported to bind to microfilaments and microtubules at the C-terminus of the protein (12).…”

Section: Discussionmentioning

confidence: 99%

Neuroepithelial stem cell marker nestin regulates the migration, invasion and growth of human gliomas

Ishiwata

Teduka²,

Yamamoto³

et al. 2011

Oncol Rep

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Abstract. Nestin, a class VI intermediate filament protein, was originally described as a neuronal stem cell marker during central nervous system development. Nestin is expressed in gliomas, and its expression levels are higher in gliomas with high WHO histopathological classification grades than in those with low grades. In the present study, we examined whether nestin regulates the biological activities of human glioma cells. Immunohistochemically, the nestin expression patterns in 10 human glioblastoma patients were examined. The expression levels of nestin in A172, a human high-grade glioma cell line, and KG-1-C, a human low-grade glioma cell line, were examined using real-time PCR, Western blot and immunofluorescence analyses. An expression vector carrying a short hairpin RNA targeting nestin was stably transfected into A172 (Sh) cells. The effects of decreased expression levels of nestin in Sh cells on cell growth, migration, invasion, adhesion to extracellular matrices and fibrillar actin expression on three-dimensional culture plates were examined. The nestin expression vector was transiently transfected into KG-1-C (Nes) cells, and the effects of the nestin overexpression on cell growth and migration were examined. Nestin was expressed in the cytoplasm of the glioblastoma cells in all cases examined. Sh cells showed marked decreases in the expression levels of nestin mRNA and protein, and the growth rate of Sh cells was lower than that of sham (Sc) cells. In contrast, the adhesion activity of Sh cells to types I and IV collagens, fibronectin and laminin was higher than that of Sc cells. Fibrillar actin was clearly detected at the periphery of colonies of Sh cells at the attachment sites on three-dimensional culture plates. The migration and invasion of Sh cells were markedly inhibited compared with those of Sc cells. In contrast, the levels of nestin expression markedly increased in the Nes cells, which were transiently transfected with the nestin expression vector. The growth rate and motility of Nes cells were higher than those of the mock cells. In conclusion, nestin plays important roles in cell growth, migration, invasion and adhesion to extra-cellular matrices in glioma cells. Nestin may serve as a novel candidate for molecular-targeted therapy for gliomas, including glioblastomas.

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“…The importance of the IF system for cell migration and process extension has become apparent in several gene knock out paradigms including keratins [Long et al, 2006], vimentin [Eckes et al, 1998;Nieminen et al, 2006], vimentin/glial fibrillary acidic protein [Lepekhin et al, 2001], and synemin [Pan et al, 2008]. The resulting altered tissue properties are apparently of relevance for wound healing [Eckes et al, 2000;Mazzalupo et al, 2003;Wong and Coulombe, 2003], homing of leukocytes [Nieminen et al, 2006], glial scar formation [Pekny et al, 1999], and axonal regeneration [Menet et al, 2003;Triolo et al, 2006;Shim et al, 2008;Toth et al, 2008].…”

Section: Discussionmentioning

confidence: 99%

Actin‐dependent dynamics of keratin filament precursors

Kölsch

Windoffer

Leube

2009

Cell Motil. Cytoskeleton

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Actin filament and microtubule growth characteristics are defined by their different plus and minus ends. In contrast, intermediate filaments lack this type of polarity. Yet, intermediate filament network growth occurs by selective addition of newly formed and polymerizing keratin particles at peripheral network domains thereby allowing polarized network reorganization. To examine this process at high resolution in living cells, mammary epithelium-derived, immortalized EpH4-cells were infected with retroviral cDNA constructs coding for human keratin 18-fluorescent protein hybrids. Several stable cell lines were established presenting characteristic fluorescent keratin filament (KF) networks. These cells contain particularly large and abundant lamellipodia in which nascent keratin particle dynamics are easily detected by time-lapse fluorescence microscopy. These keratin particles originate close to the plasma membrane, translocate continuously toward the cell center, and integrate end-on into the peripheral KF network. We show that this inward-directed transport relies on intact actin filaments. After treatment with the actin filament-disrupting drug cytochalasin newly polymerizing keratin assemblies still appear in the peripheral cytoplasm but remain stationary. On the other hand, nocodazole-mediated disruption of microtubules does not affect the centripetal KF precursor transport. From these and other observations a model is deduced which postulates that focal adhesion-dependent keratin polymerization occurs in forming lamellipodia and that transport of newly formed keratin particles is mediated by actin filaments until network integration. This mechanism allows extension of the KF network toward the leading edge in migrating cells and may be of relevance for tissue development and regeneration.

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Intermediate filament protein synemin contributes to the migratory properties of astrocytoma cells by influencing the dynamics of the actin cytoskeleton

Cited by 42 publications

References 43 publications

Nestin is a novel target for suppressing pancreatic cancer cell migration, invasion and metastasis

Nestin is a novel target for suppressing pancreatic cancer cell migration, invasion and metastasis

Neuroepithelial stem cell marker nestin regulates the migration, invasion and growth of human gliomas

Actin‐dependent dynamics of keratin filament precursors

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