scholarly journals The Neuronal Differentiation Factor NeuroD1 Downregulates the Neuronal Repellent Factor Slit2 Expression and Promotes Cell Motility and Tumor Formation of Neuroblastoma

2011 ◽  
Vol 71 (8) ◽  
pp. 2938-2948 ◽  
Author(s):  
Peng Huang ◽  
Satoshi Kishida ◽  
Dongliang Cao ◽  
Yuko Murakami-Tonami ◽  
Ping Mu ◽  
...  
Keyword(s):  
Cell Motility ◽  
Neuronal Differentiation ◽  
Tumor Formation ◽  
Differentiation Factor

scholarly journals Role of the V1G1 subunit of V-ATPase in breast cancer cell migration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria De Luca ◽  
Roberta Romano ◽  
Cecilia Bucci
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Motility ◽  
Cancer Progression ◽  
Tumor Formation ◽  
Downstream Signaling ◽  
Late Endosomes ◽  
Intracellular Compartments

AbstractV-ATPase is a large multi-subunit complex that regulates acidity of intracellular compartments and of extracellular environment. V-ATPase consists of several subunits that drive specific regulatory mechanisms. The V1G1 subunit, a component of the peripheral stalk of the pump, controls localization and activation of the pump on late endosomes and lysosomes by interacting with RILP and RAB7. Deregulation of some subunits of the pump has been related to tumor invasion and metastasis formation in breast cancer. We observed a decrease of V1G1 and RAB7 in highly invasive breast cancer cells, suggesting a key role of these proteins in controlling cancer progression. Moreover, in MDA-MB-231 cells, modulation of V1G1 affected cell migration and matrix metalloproteinase activation in vitro, processes important for tumor formation and dissemination. In these cells, characterized by high expression of EGFR, we demonstrated that V1G1 modulates EGFR stability and the EGFR downstream signaling pathways that control several factors required for cell motility, among which RAC1 and cofilin. In addition, we showed a key role of V1G1 in the biogenesis of endosomes and lysosomes. Altogether, our data describe a new molecular mechanism, controlled by V1G1, required for cell motility and that promotes breast cancer tumorigenesis.

scholarly journals Modulation of Cellular Migration and Survival by c-Myc through the Downregulation of Urokinase (uPA) and uPA Receptor

2010 ◽  
Vol 30 (7) ◽  
pp. 1838-1851 ◽  
Author(s):  
Daniela Alfano ◽  
Giuseppina Votta ◽  
Almut Schulze ◽  
Julian Downward ◽  
Mario Caputi ◽  
...  
Keyword(s):  
Cell Motility ◽  
Cellular Transformation ◽  
Tumor Formation ◽  
Cellular Migration ◽  
Epithelial Cell Line ◽  
Cellular Motility ◽  
Upa Receptor ◽  
Upar Expression ◽  
Repressive Effect ◽  
Cell Invasiveness

ABSTRACT It has been proposed that c-Myc proapoptotic activity accounts for most of its restraint of tumor formation. We established a telomerase-immortalized human epithelial cell line expressing an activatable c-Myc protein. We found that c-Myc activation induces, in addition to increased sensitivity to apoptosis, reductions in cell motility and invasiveness. Transcriptome analysis revealed that urokinase (uPA) and uPA receptor (uPAR) were strongly downregulated by c-Myc. Evidence is provided that the repression of uPA and uPAR may account for most of the antimigratory and proapoptotic activities of c-Myc. c-Myc is known to cooperate with Ras in cellular transformation. We therefore investigated if this cooperation could converge in the control of uPA/uPAR expression. We found that Ras is able to block the effects of c-Myc activation on apoptosis and cellular motility but not on cell invasiveness. Accordingly, the activation of c-Myc in the context of Ras expression had only minor influence on uPAR expression but still had a profound repressive effect on uPA expression. Thus, the differential regulation of uPA and uPAR by c-Myc and Ras correlates with the effects of these two oncoproteins on cell motility, invasiveness, and survival. In conclusion, we have discovered a novel link between c-Myc and uPA/uPAR. We propose that reductions of cell motility and invasiveness could contribute to the inhibition of tumorigenesis by c-Myc and that the regulation of uPA and uPAR expression may be a component of the ability of c-Myc to reduce motility and invasiveness.

Expression of mRNA for a neuronal differentiation factor, TA20, in developing rat brains

1996 ◽  
Vol 24 (4) ◽  
pp. 421-425 ◽  
Author(s):  
Chihiro Tohda ◽  
Shinobu Nagai ◽  
Yasushi Kuraishi ◽  
Yasuyuki Nomura
Keyword(s):  
Neuronal Differentiation ◽  
Differentiation Factor ◽  
Developing Rat

De novo pathogenic variants in neuronal differentiation factor 2 (NEUROD2) cause a form of early infantile epileptic encephalopathy

2018 ◽  
Vol 56 (2) ◽  
pp. 113-122 ◽  
Author(s):  
Annalisa G Sega ◽  
Emily K Mis ◽  
Kristin Lindstrom ◽  
Saadet Mercimek-Andrews ◽  
Weizhen Ji ◽  
...  
Keyword(s):  
Genome Editing ◽  
Candidate Genes ◽  
Neuronal Differentiation ◽  
Protein Function ◽  
De Novo ◽  
Single Gene ◽  
Epileptic Encephalopathy ◽  
Epileptic Encephalopathies ◽  
Differentiation Factor

BackgroundEarly infantile epileptic encephalopathies are severe disorders consisting of early-onset refractory seizures accompanied often by significant developmental delay. The increasing availability of next-generation sequencing has facilitated the recognition of single gene mutations as an underlying aetiology of some forms of early infantile epileptic encephalopathies.ObjectivesThis study was designed to identify candidate genes as a potential cause of early infantile epileptic encephalopathy, and then to provide genetic and functional evidence supporting patient variants as causative.MethodsWe used whole exome sequencing to identify candidate genes. To model the disease and assess the functional effects of patient variants on candidate protein function, we used in vivo CRISPR/Cas9-mediated genome editing and protein overexpression in frog tadpoles.ResultsWe identified novel de novo variants in neuronal differentiation factor 2 (NEUROD2) in two unrelated children with early infantile epileptic encephalopathy. Depleting neurod2 with CRISPR/Cas9-mediated genome editing induced spontaneous seizures in tadpoles, mimicking the patients’ condition. Overexpression of wild-type NEUROD2 induced ectopic neurons in tadpoles; however, patient variants were markedly less effective, suggesting that both variants are dysfunctional and likely pathogenic.ConclusionThis study provides clinical and functional support for NEUROD2 variants as a cause of early infantile epileptic encephalopathy, the first evidence of human disease caused by NEUROD2 variants.

CLL, but not normal, B cells are dependent on autocrine VEGF and α4β1 integrin for chemokine-induced motility on and through endothelium

Blood ◽  
2005 ◽  
Vol 105 (12) ◽  
pp. 4813-4819 ◽  
Author(s):  
Kathleen J. Till ◽  
David G. Spiller ◽  
Robert J. Harris ◽  
Haijuan Chen ◽  
Mirko Zuzel ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Motility ◽  
Vascular Endothelial Cell ◽  
Cell Movement ◽  
Tumor Formation ◽  
Lymphocytic Leukemia ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Malignant Cells ◽  
Autocrine Loop

Abstract Vascular endothelial cell growth factor (VEGF) is a multifunctional cytokine involved in tumor formation. In chronic lymphocytic leukemia (CLL), it is known that the malignant cells secrete VEGF and possess VEGF receptors. This suggests that an autocrine loop might be important in the pathogenesis of CLL. Here we show that, in patients with lymphadenopathy, autocrine VEGF and α4β1 integrin are involved in the chemokine-dependent motility of CLL cells on and through endothelium—processes important for the invasion of lymphoreticular tissues, a major determinant of disease outcome. In contrast, normal lymphocytes were not dependent on autocrine VEGF or α4β1 for either type of cell movement. Moreover, in contrast to normal B lymphocytes, CLL cells failed to cluster and activate αLβ2 in response to chemokines, unless VEGF receptor(s) and α4β1 were also engaged by their respective ligands. This is the first demonstration that autocrine VEGF is involved in CLL-cell motility, and that the αLβ2 on the malignant cells is functionally altered compared with that of normal B cells in not undergoing activation in response to chemokine alone. Given the importance of cell motility for tissue invasion, the present results provide a rationale for a trial of VEGF and α4 blockade in patients with CLL who have tissue disease. (Blood. 2005;105:4813-4819)

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