SMN deficiency attenuates migration of U87MG astroglioma cells through the activation of RhoA

Caraballo-Miralles, Víctor; Cardona-Rossinyol, Andrea; Garcerá, Ana; Villalonga, Priam; Soler, Rosa M.; Olmos, Gabriel; Lladó, Jerònia

doi:10.1016/j.mcn.2011.12.003

Cited by 24 publications

(22 citation statements)

References 61 publications

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“…Treatment with Y27632 resulted in a two-fold increase in cell migration in glioma cells. Moreover, ROCK activation causes a shift from filamentous to monomeric actin, leading to the disappearance of stress fibers in human U87MG glioma cells [13]. In the present study, caffeine induced MLC phosphorylation and stress fiber disassembly, indicating the involvement of ROCK in caffeine's effects on glioma cells.…”

Section: Discussionsupporting

confidence: 57%

“…Furthermore, rho -associated protein kinase ( ROCK ) and myosin light chain kinase (MLCK) both contribute to the phosphorylated myosin light chain (MLC), decreasing the turnover of focal complexes and cell migration in fibroblasts [12]. In human glioblastoma cells, ROCK activation decreases cell migration and impairs the balance of F- and G-actin [13]. The focal adhesion complex may be a potential treatment target for glioblastoma.…”

Section: Introductionmentioning

confidence: 99%

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Caffeine Inhibits Migration in Glioma Cells through the ROCK-FAK Pathway

Chen

Chou

Ding

et al. 2014

Cell Physiol Biochem

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Aims: Glioma is the most malignant brain tumor that has the ability to migrate and invade the CNS. In this study, we investigated the signaling mechanism of caffeine on the migration of glioma cells. Methods: The effect of caffeine on cell migration was evaluated using Transwell and wound healing assays. The expression of the focal adhesion complex as it related to cell migration was assayed using Western blotting and immunostaining. Results: Caffeine decreased the migration of rat C6 and human U87MG glioma cells and down-regulated the expression of phosphorylated focal adhesion kinase (p-FAK) and p-paxillin. Caffeine also decreased p-FAK staining at the edge of glioma cells and disassembled actin stress fibers. Additionally, caffeine elevated expression of phosphorylated myosin light chain (p-MLC), an effect that could be blocked by Y27632, a rho-associated protein kinase (ROCK) inhibitor, but not myosin light chain kinase inhibitor, ML-7. Y27632 also inhibited the caffeine-reduced expression of p-FAK and p-paxillin as well as cell migration. Conclusion: Caffeine decreased the migration of glioma cell through the ROCK-focal adhesion complex pathway; this mechanism may be useful as part of clinical therapy in the future.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Caffeine Inhibits Migration in Glioma Cells through the ROCK-FAK Pathway

Chen

Chou

Ding

et al. 2014

Cell Physiol Biochem

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“…In addition to defects within myelinating Schwann cells, there is a loss of nerve capping terminal Schwann cells at the NMJs of intermediate SMA mice (Murray et al, 2013) that might suggest a defect in migration of Schwann cells to the endplate. While we cannot exclude the fact that Smn depletion may simply reduce the survival of terminal Schwann cells, the former hypothesis is of interest since Smn-depleted astroglioma U897MG cells display a RhoA/ROCK-dependent delay in migration (Caraballo-Miralles et al, 2012). Indeed, these cells express significantly more activated RhoA and downstream effector MLC.…”

Section: Glial Cellsmentioning

confidence: 99%

“…The caveat of this study is that it was performed in a cell line and to date, there is no evidence of glial migration abnormalities in in vivo models of SMA or in primary cultures of Smn-depleted astrocytes and Schwann cells. Nevertheless, the studies on U897MG cells and nerve capping terminal Schwann cells (Caraballo-Miralles et al, 2012; Murray et al, 2013) raise the possibility that RhoA/ROCK-dependent glial cell migration is affected in SMA, thus warranting further examination of this aspect in future investigations.…”

Section: Glial Cellsmentioning

confidence: 99%

“…Thus, systemic administration of Y-27632 or Fasudil to SMA mice may improve Schwann cell migration, subsequently enhancing the myelination potential of Schwann cells and/or adequate nerve capping at the NMJ. Indeed, the migration delay in Smn-depleted U897MG astroglioma cells is corrected following treatment with Y-27632 (Caraballo-Miralles et al, 2012). Alternatively, treating primary dorsal root ganglion (DRG) cultures with Y-27632 promotes neurite outgrowth in a Schwann cell-dependent fashion (Fuentes et al, 2008).…”

Section: Glial Cellsmentioning

confidence: 99%

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ROCK inhibition as a therapy for spinal muscular atrophy: understanding the repercussions on multiple cellular targets

2014

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Spinal muscular atrophy (SMA) is the most common genetic disease causing infant death, due to an extended loss of motoneurons. This neuromuscular disorder results from deletions and/or mutations within the Survival Motor Neuron 1 (SMN1) gene, leading to a pathological decreased expression of functional full-length SMN protein. Emerging studies suggest that the small GTPase RhoA and its major downstream effector Rho kinase (ROCK), which both play an instrumental role in cytoskeleton organization, contribute to the pathology of motoneuron diseases. Indeed, an enhanced activation of RhoA and ROCK has been reported in the spinal cord of an SMA mouse model. Moreover, the treatment of SMA mice with ROCK inhibitors leads to an increased lifespan as well as improved skeletal muscle and neuromuscular junction pathology, without preventing motoneuron degeneration. Although motoneurons are the primary target in SMA, an increasing number of reports show that other cell types inside and outside the central nervous system contribute to SMA pathogenesis. As administration of ROCK inhibitors to SMA mice was systemic, the improvement in survival and phenotype could therefore be attributed to specific effects on motoneurons and/or on other non-neuronal cell types. In the present review, we will present the various roles of the RhoA/ROCK pathway in several SMA cellular targets including neurons, myoblasts, glial cells, cardiomyocytes and pancreatic cells as well as discuss how ROCK inhibition may ameliorate their health and function. It is most likely a concerted influence of ROCK modulation on all these cell types that ultimately lead to the observed benefits of pharmacological ROCK inhibition in SMA mice.

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PFN1 mutations are also rare in the Catalan population with amyotrophic lateral sclerosis

et al. 2014

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Evidence of genetic heterogeneity in ALS has been found, with at least 31 genes being identified to date as causing ALS, and other genes being suggested as risk factors for susceptibility to the disease and for phenotype modifications. In recent years, new molecular genetic methodologies, especially GWAS and exome sequencing, have contributed to the identification of new ALS genes. Some of these genes (SOD1, TARDBP, FUS, and C9orf72) have homogenous frequencies in different populations. However, a few genes are rare in populations other than those in which they were first identified. Here we investigate the frequency of the PFN1 gene in a Catalan ALS population. A mutational analysis of the PFN1 gene was carried out on a Catalan cohort of 42 ALS families (FALS) and 423 sporadic ALS patients (SALS). The screening included 600 healthy controls. No PFN1 mutations were identified in either the FALS or SALS group. We also found no mutations in the control group. Our results are consistent with those described in other populations with very low frequencies, suggesting that PFN1 is a very rare cause of ALS worldwide. Together with the absence of a distinctive phenotype associated with ALS18, these results mean that this gene should be a second or third line for inclusion in screening in patients requesting genetic counseling.

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SMN deficiency attenuates migration of U87MG astroglioma cells through the activation of RhoA

Cited by 24 publications

References 61 publications

Caffeine Inhibits Migration in Glioma Cells through the ROCK-FAK Pathway

Caffeine Inhibits Migration in Glioma Cells through the ROCK-FAK Pathway

ROCK inhibition as a therapy for spinal muscular atrophy: understanding the repercussions on multiple cellular targets

PFN1 mutations are also rare in the Catalan population with amyotrophic lateral sclerosis

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