Molecular evolution of type VI intermediate filament proteins

Guérette, Dominique; Khan, Paul A.; Savard, Pierre; Vincent, Michel

doi:10.1186/1471-2148-7-164

Cited by 86 publications

(77 citation statements)

References 45 publications

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“…Nestin, a class VI intermediate filament, similarly to other eukaryotic intermediate filaments, connects the 3 components of the cytoskeleton and coordinates changes in the cell dynamics (49,50). Nestin reportedly interacts with vimentin or desmin to form heterodimers or polymers; these structures provide cellular mechanostructural support, maintain cellular membranes, and restrict organelles to a limited area (51).…”

Section: Discussionmentioning

confidence: 99%

Stem Cell Marker Nestin Is Critical for TGF-β1-Mediated Tumor Progression in Pancreatic Cancer

Weng

Hsiao

et al. 2013

Molecular Cancer Research

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The stem cell marker nestin is an intermediate filament protein that plays an important role in cell integrity, migration, and differentiation. Nestin expression occurs in approximately one third of pancreatic ductal adenocarcinoma (PDAC), and its expression strongly correlates with tumor staging and metastasis. Little is known about the mechanisms by which nestin influences PDAC progression. Here, nestin overexpression in PDAC cells increased cell motility and drove phenotypic changes associated with the epithelial-mesenchymal transition (EMT) in vitro; conversely, knockdown of endogenous nestin expression reduced the migration rate and reverted cells to a more epithelial phenotype. Mouse xenograft studies showed that knockdown of nestin significantly reduced tumor incidence and volume. Nestin protein expression was associated with Smad4 status in PDAC cells; hence, nestin expression might be regulated by the TGF-b1/Smad4 pathway in PDAC. We examined nestin expression after TGF-b1 treatment in human pancreatic cancer PANC-1 and PANC-1 shSmad4 cells. The TGF-b1/Smad4 pathway induced nestin protein expression in PDAC cells in a Smad4-dependent manner. Moreover, increased nestin expression caused a positive feedback regulator of the TGF-b1 signaling system. In addition, hypoxia was shown to induce nestin expression in PDAC cells, and the hypoxiainduced expression of nestin is mediated by the TGF-b1/Smad4 pathway. Finally, the antimicrotubule inhibitors, cytochalasin D and withaferin A, exhibited anti-nestin activity; these inhibitors might be potential antimetastatic drugs. Our findings uncovered a novel role of nestin in regulating TGF-b1-induced EMT. Antinestin therapeutics may serve as a potential treatment for PDAC metastasis. Mol Cancer Res; 11(7); 768-79. Ó2013 AACR. IntroductionThe incidence of pancreatic ductal adenocarcinoma (PDAC) is rising to the fifth leading cause of cancerrelated mortality. The condition is associated with the poorest prognosis among all gastrointestinal cancers, with a 5-year survival rate less than 4% (1, 2). A main reason for this extremely poor prognosis is the cancer's tendency to invade adjacent tissues and metastasize to regional lymph at a relatively early stage. Patients with PDAC frequently

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Section: Discussionmentioning

confidence: 99%

Stem Cell Marker Nestin Is Critical for TGF-β1-Mediated Tumor Progression in Pancreatic Cancer

Weng

Hsiao

et al. 2013

Molecular Cancer Research

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“…Despite their differing sequences, the rod domain of all IF proteins contains four alpha-helix regions with long heptad repeat substructures that are predicted to form coiled coils. Analysis of the evolutionary history of the IF proteins fits a model in which type VI proteins form a branch distinct from neurofilament (NF) proteins, composed of two large proteins, synemin and nestin [8].…”

Section: Introductionmentioning

confidence: 99%

Synemin Isoforms in Astroglial and Neuronal Cells from Human Central Nervous System

Izmiryan¹,

Peltekian²,

Paulin³

et al. 2009

Neurochem Res

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The intermediate filament (IF) synemin gene encodes three IF proteins (H 180, M 150, L 41 kDa) with overlapping distributions. Synemin M was present early with vimentin and nestin. Synemin H was found later in the nervous system and mesodermic derivatives concomitantly with angiogenesis and the migration of neural crest cells. Synemin L appeared later in neurons. A series of in vitro cell cultures were done to identify the linkage between synemin isoforms and specific cell types of the central nervous system (CNS). The neurons and glia from the brains of humans and rats were cultured and double immunostaining done with antibodies against the H/M or L synemin isoforms and neural cell types (betaIII-tubulin or NeuN) or astrocyte intermediate filaments (GFAP or vimentin). In neurons of the CNS, synemin H/M were co-expressed with GFAP, vimentin or nestin in glial cells, whereas synemin L was found in neurons.

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“…Transitin in birds and nestin in mammals are type VI IF proteins that are co-expressed with vimentin in the precursor cells of the myogenic and neurogenic lineages (Chabot and Vincent, 1990;Lendahl et al, 1990;Cossette and Vincent, 1991;Sejersen and Lendahl, 1993;McCabe et al, 1995). Transitin has recently been analyzed in silico as an avian ortholog of nestin (Guérette et al, 2007). Nonetheless, the role of both proteins in embryogenesis remains incompletely understood.…”

Section: Discussionmentioning

confidence: 99%

“…The characterization of the chicken transitin gene revealed a strong relationship to the nestin IF class (Napier et al, 1999) but the C-terminal domain of transitin differs from nestin and contains a unique leucin zipper-like heptad repeat motif (HR domain) unrelated to the repeat motif found in nestin tail domain (Yuan et al, 1997;Napier et al, 1999). Nonetheless, the avian transitin and its splicing variant paranemin (Hemken et al, 1997) are orthologs of the mammalian nestin gene family (Guérette et al, 2007). These proteins are co-expressed with vimentin in most precursor cells of the neural and muscle tissues before the acquisition of a terminal IF protein typical of the fully differentiated state.…”

Section: Introductionmentioning

confidence: 99%

Transitin is required for the differentiation of avian QM7 myoblasts into myotubes

Jalouli

Lapierre

Guérette

et al. 2010

Developmental Dynamics

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*Transitin is a nestin-like intermediate filament protein co-expressed with vimentin in the precursor cells of the myogenic and neurogenic lineages of the avian embryo. To understand its role in myogenesis, stable cell lines expressing transitin-targeted siRNAs were derived from the quail muscle cell line QM7. When cells were cultured in differentiation medium, we found that transitin knockdown prevented myoblast fusion and myotube formation. MyoD mRNA could be detected in transitin siRNA-transfected cells, but upregulation of myogenin and desmin expression was impaired compared to control cells. In addition, transitin siRNA cells maintain high levels of Pax7 expression suggesting that QM7 myoblasts into which transitin expression has been attenuated display a muscle progenitor cell phenotype (Pax7). These observations indicate that transitin plays an important role in the initiation of the myogenic program in avian muscle progenitor cells in acting downstream of MyoD and upstream of myogenin during the lineage progression. V C

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Molecular evolution of type VI intermediate filament proteins

Cited by 86 publications

References 45 publications

Stem Cell Marker Nestin Is Critical for TGF-β1-Mediated Tumor Progression in Pancreatic Cancer

Stem Cell Marker Nestin Is Critical for TGF-β1-Mediated Tumor Progression in Pancreatic Cancer

Synemin Isoforms in Astroglial and Neuronal Cells from Human Central Nervous System

Transitin is required for the differentiation of avian QM7 myoblasts into myotubes

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