scholarly journals Sphingosine 1-Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Mesenchymal Cell Migration through S1P Activation of Complementary Kinase Pathways

2013 ◽  
Vol 288 (8) ◽  
pp. 5398-5406 ◽  
Author(s):  
Patrick Quint ◽  
Ming Ruan ◽  
Larry Pederson ◽  
Moustapha Kassem ◽  
Jennifer J. Westendorf ◽  
...  
Keyword(s):  
Cell Migration ◽  
Mesenchymal Cell ◽  
S1p Receptors ◽  
Sphingosine 1 Phosphate

Mechanics and Mechanisms of 3D Mesenchymal Cell Migration

2020 ◽  
Author(s):  
Andrew D. Doyle ◽  
Daniel J. Sykora ◽  
Gustavo G. Pacheco ◽  
Matthew L. Kutys ◽  
Kenneth M. Yamada
Keyword(s):  
Cell Migration ◽  
Mesenchymal Cell

2-Aryl(pyrrolidin-4-yl)acetic acids are potent agonists of sphingosine-1-phosphate (S1P) receptors

2006 ◽  
Vol 16 (13) ◽  
pp. 3564-3568 ◽  
Author(s):  
Lin Yan ◽  
Richard Budhu ◽  
Pei Huo ◽  
Christopher L. Lynch ◽  
Jeffrey J. Hale ◽  
...  
Keyword(s):  
S1p Receptors ◽  
Sphingosine 1 Phosphate ◽  
Acetic Acids

scholarly journals Different translation dynamics of β-and γ-actin regulates cell migration

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Pavan Vedula ◽  
Satoshi Kurosaka ◽  
Brittany MacTaggart ◽  
Qin Ni ◽  
Garegin Papoian ◽  
...  
Keyword(s):  
Cell Migration ◽  
Amino Acid ◽  
Single Molecule ◽  
Amino Acid Level ◽  
Focal Adhesions ◽  
Mesenchymal Cell ◽  
Cell Periphery ◽  
Pronounced Difference ◽  
Coding Sequence

β- and γ-cytoplasmic actins are ubiquitously expressed in every cell type and are nearly identical at the amino acid level but play vastly different roles in vivo. Their essential roles in embryogenesis and mesenchymal cell migration critically depend on the nucleotide sequences of their genes, rather than their amino acid sequence, however it is unclear which gene elements underlie this effect. Here we address the specific role of the coding sequence in β- and γ-cytoplasmic actins' intracellular functions, using stable polyclonal populations of immortalized mouse embryonic fibroblasts with exogenously expressed actin isoforms and their 'codon-switched' variants. When targeted to the cell periphery using the β-actin 3′UTR, β-actin and γ-actin have differential effects on cell migration. These effects directly depend on the coding sequence. Single molecule measurements of actin isoform translation, combined with fluorescence recovery after photobleaching, demonstrate a pronounced difference in β- and γ-actins' translation elongation rates in cells, leading to changes in their dynamics at the focal adhesions, impairments in actin bundle formation, and reduced cell anchoring to the substrate during migration. Our results demonstrate that coding sequence-mediated differences in actin translation play a key role in cell migration.

scholarly journals Modulating Sphingosine-1-Phosphate receptors to improve chemotherapy delivery to Ewing sarcoma

2019 ◽  
Author(s):  
Enrica Marmonti ◽  
Hannah Savage ◽  
Aiqian Zhang ◽  
Claudia Alvarez ◽  
Miriam Morrell ◽  
...  
Keyword(s):  
G Protein ◽  
Ewing Sarcoma ◽  
Tyrosine Kinases ◽  
Tumor Vasculature ◽  
Cell Junction ◽  
Tumor Vessels ◽  
S1p Receptors ◽  
Vessel Permeability ◽  
Sphingosine 1 Phosphate ◽  
G Protein Coupled

ABSTRACTTumor vasculature is innately dysfunctional. Poorly functional tumor vessels inefficiently deliver chemotherapy to tumor cells; vessel hyper-permeability promotes chemotherapy delivery primarily to a tumor’s periphery. Here we identify a method for enhancing chemotherapy delivery and efficacy in Ewing sarcoma (ES) in mice by modulating tumor vessel permeability. Vessel permeability is partially controlled by the G protein-coupled Sphinosine-1-phosphate receptors 1 and 2 (S1PR1 and S1PR2) on endothelial cells. S1PR1 promotes endothelial cell junction integrity while S1PR2 destabilizes it. We hypothesize that an imbalance of S1PR1:S1PR2 is partially responsible for the dysfunctional vascular phenotype characteristic of ES and that by altering the balance in favor of S1PR1, ES vessel hyper-permeability can be reversed. In this study, we demonstrate that pharmacologic activation of S1PR1 by SEW2871 or inhibition of S1PR2 by JTE-013 caused more organized, mature, and functional tumor vessels. Importantly, S1PR1 activation or S1PR2 inhibition improved chemotherapy delivery to the tumor and anti-tumor efficacy. Our data suggests that pharmacologic targeting of S1PR1 and S1PR2 may be a useful adjuvant to standard chemotherapy for ES patients.NOVELTY AND IMPACTThis study demonstrates that Sphingosine-1-Phosphate (S1P) receptors are potential novel targets for tumor vasculature remodeling and adjuvant therapy for the treatment of Ewing Sarcoma. Unlike receptor tyrosine kinases that have already been extensively evaluated for use as vascular normalizing agents in oncology, S1P receptors are G protein-coupled receptors, which have not been well studied in tumor endothelium. Pharmacologic activators and inhibitors of S1P receptors are currently in clinical trials for treatment of auto-immune and cardiovascular diseases, indicating potential for clinical translation of this work.

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