Involvement of Focal Adhesion Kinase in Inhibition of Motility of Human Breast Cancer Cells by Sphingosine 1-Phosphate

Wang, Fang; Nohara, Keiko; Olivera, Ana; Thompson, Erik W.; Spiegel, Sarah

doi:10.1006/excr.1998.4327

Cited by 64 publications

(51 citation statements)

References 47 publications

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“…Cellular mechanisms by which the chemorepellants suppress cell migration have remained largely unknown. S1P is unique and distinct from these chemorepellants in that it bidirectionally regulates cell migration, i.e., S1P acts as a chemoattractant for certain cell types (34,40,41,73), while it strongly inhibits cell migration in others (12,31,59,72,77); the latter include several tumorderived cell types. S1P is a normal constituent of the blood and is present at a substantially high concentration (Ͼ0.1 M), most of which is bound to albumin (79).…”

Section: Discussionmentioning

confidence: 99%

“…1A). It was previously demonstrated that human vascular smooth muscle cells (12) and certain tumor cells including B16 melanoma cells (59,72,74,77) respond to S1P with inhibition of directed cell migration. We identified EDG5 as a dominant EDG subtype expressed in vascular smooth muscle cells and B16 melanoma cells (H. Okamoto, H. Yamaguchi, Y. Ryu, and Y. Takuwa, unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it was shown that sphingosine, a precursor of S1P, could alter cellular PAK activity (11) and PDK1 activity (33). It was also noted that higher concentrations of S1P are required for inhibition of cell motility in breast cancer cells (72,74) than in vascular smooth muscle cells (12) and B16 melanoma cells (59,77). Moreover, dihydro-S1P, an agonist for the EDG S1P receptors (70,71), is ineffective in inhibiting the motility of the breast cancer cells (74), which contrasts with the present data for CHO-EDG5 cells (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…Strikingly, S1P inhibits, rather than stimulates, the migration of vascular smooth muscle cells (12) and neutrophils (31) and also the invasiveness of some tumor cells including melanoma cells (59,77), osteosarcoma cells (59), and breast carcinoma cells (72,74). The inhibitory actions of S1P on motility of melanoma cells are suggested to be mediated by cell surface action, because immobilized S1P inhibits migration as effectively as soluble S1P (77).…”

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confidence: 99%

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Inhibitory Regulation of Rac Activation, Membrane Ruffling, and Cell Migration by the G Protein-Coupled Sphingosine-1-Phosphate Receptor EDG5 but Not EDG1 or EDG3

Okamoto

Takuwa

Yokomizo

et al. 2000

Molecular and Cellular Biology

306

303

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Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that induces a variety of biological responses in diverse cell types. Many, if not all, of these responses are mediated by members of the EDG (endothelial differentiation gene) family G protein-coupled receptors EDG1, EDG3, and EDG5 (AGR16). Among prominent activities of S1P is the regulation of cell motility; S1P stimulates or inhibits cell motility depending on cell types. In the present study, we provide evidence for EDG subtype-specific, contrasting regulation of cell motility and cellular Rac activity. In CHO cells expressing EDG1 or EDG3 (EDG1 cells or EDG3 cells, respectively) S1P as well as insulin-like growth factor I (IGF I) induced chemotaxis and membrane ruffling in phosphoinositide (PI) 3-kinase-and Rac-dependent manners. Both S1P and IGF I induced a biphasic increase in the amount of the GTP-bound active form of Rac. In CHO cells expressing EDG5 (EDG5 cells), IGF I similarly stimulated cell migration; however, in contrast to what was found for EDG1 and EDG3 cells, S1P did not stimulate migration but totally abolished IGF I-directed chemotaxis and membrane ruffling, in a manner dependent on a concentration gradient of S1P. In EDG5 cells, S1P stimulated PI 3-kinase activity as it did in EDG1 cells but inhibited the basal Rac activity and totally abolished IGF I-induced Rac activation, which involved stimulation of Rac-GTPase-activating protein activity rather than inhibition of Rac-guanine nucleotide exchange activity. S1P induced comparable increases in the amounts of GTP-RhoA in EDG3 and EDG5 cells. Neither S1P nor IGF I increased the amount of GTP-bound Cdc42. However, expression of N 17 -Cdc42, but not N 19 -RhoA, suppressed S1P-and IGF I-directed chemotaxis, suggesting a requirement for basal Cdc42 activity for chemotaxis. Taken together, the present results demonstrate that EDG5 is the first example of a hitherto-unrecognized type of receptors that negatively regulate Rac activity, thereby inhibiting cell migration and membrane ruffling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Inhibitory Regulation of Rac Activation, Membrane Ruffling, and Cell Migration by the G Protein-Coupled Sphingosine-1-Phosphate Receptor EDG5 but Not EDG1 or EDG3

Okamoto

Takuwa

Yokomizo

et al. 2000

Molecular and Cellular Biology

306

303

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“…6,7 Each S1P receptor displays a unique tissue expression pattern and is coupled to a distinct set of G proteins (G i/o , G q and G 12/13 ), leading to the activation of receptor-specific intracellular signaling pathways. 6 S1P affects the proliferation, motility and invasiveness of malignant cells and can mediate proliferative 8,9 or antiproliferative 10,11 behavior in cancer cells. The various effects of S1P may be attributed to the diversity of its receptors.…”

mentioning

confidence: 99%

Sphingosine‐1‐phosphate receptor type 1 regulates glioma cell proliferation and correlates with patient survival

Yoshida¹,

Nakada²,

Sugimoto³

et al. 2010

Intl Journal of Cancer

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Sphingosine-1-phosphate (S1P) is a bioactive lipid that signals through a family of G protein-coupled receptors consisting of 5 members termed S1P 1-5 , and it regulates cellular proliferation, migration and survival. We investigated the expression and role of S1P receptors in glioma. Human glioma expressed S1P 1 , S1P 2 , S1P 3 , and S1P 5 by quantitative real-time PCR analysis. Expression of the S1P 1 was significantly lower in glioblastoma than in the normal brain (p < 0.01) and diffuse astrocytoma (p < 0.05). Immunoblotting showed that normal brain expressed more S1P 1 protein than did glioblastoma. Immunohistochemistry showed that S1P 1 was localized predominantly in the astrocytes in the normal brain, but no staining was observed in glioblastoma. Downregulation of S1P 1 expression correlated with poor survival of patients with glioblastoma (p < 0.05). S1P 1 small interfering RNA promoted cell proliferation in high-expressor glioma cell lines (T98G, G112). Cell proliferation was promoted by the pertussis toxin, which deactivates G i/o type of G proteins; the S1P 1 is exclusively coupled to these proteins. Forced expression of the S1P 1 in low-expressor cell lines (U87, U251) resulted in decreased cell growth and led to suppressed tumor growth in transplanted gliomas in vivo. Furthermore, we found a significant association between the S1P 1 expression and early growth response-1, a transcriptional factor that exhibits tumor suppression in glioblastoma cells (p < 0.05). These data indicate that the downregulation of S1P 1 expression enhances the malignancy of glioblastoma by increasing cell proliferation and correlates with the shorter survival of patients with glioblastoma.

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Sphingosine‐1‐phosphate plays a role in the suppression of lateral pseudopod formation during Dictyostelium discoideum cell migration and chemotaxis

Kumar

Wessels

Daniels

et al. 2004

Cell Motil. Cytoskeleton

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Sphingosine-1-phosphate (S-1-P) is a bioactive lipid that plays a role in diverse biological processes. It functions both as an extracellular ligand through a family of high-affinity G-protein-coupled receptors, and intracellularly as a second messenger. A growing body of evidence has implicated S-1-P in controlling cell movement and chemotaxis in cultured mammalian cells. Mutant D. discoideum cells, in which the gene encoding the S-1-P lyase had been specifically disrupted by homologous recombination, previously were shown to be defective in pseudopod formation, suggesting that a resulting defect might exist in motility and/or chemotaxis. To test this prediction, we analyzed the behavior of mutant cells in buffer, and in both spatial and temporal gradients of the chemoattractant cAMP, using computer-assisted 2-D and 3-D motion analysis systems. Under all conditions, S-1-P lyase null mutants were unable to suppress lateral pseudopod formation like wild-type control cells. This resulted in a reduction in velocity in buffer and spatial gradients of cAMP. Mutant cells exhibited positive chemotaxis in spatial gradients of cAMP, but did so with lowered efficiency, again because of their inability to suppress lateral pseudopod formation. Mutant cells responded normally to simulated temporal waves of cAMP but mimicked the temporal dynamics of natural chemotactic waves. The effect must be intracellular since no homologs of the S-1-P receptors have been identified in the Dictyostelium genome. The defects in the S-1-P lyase null mutants were similar to those seen in mutants lacking the genes for myosin IA, myosin IB, and clathrin, indicating that S-1-P signaling may play a role in modulating the activity or organization of these cytoskeletal elements in the regulation of lateral pseudopod formation.

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Involvement of Focal Adhesion Kinase in Inhibition of Motility of Human Breast Cancer Cells by Sphingosine 1-Phosphate

Cited by 64 publications

References 47 publications

Inhibitory Regulation of Rac Activation, Membrane Ruffling, and Cell Migration by the G Protein-Coupled Sphingosine-1-Phosphate Receptor EDG5 but Not EDG1 or EDG3

Inhibitory Regulation of Rac Activation, Membrane Ruffling, and Cell Migration by the G Protein-Coupled Sphingosine-1-Phosphate Receptor EDG5 but Not EDG1 or EDG3

Sphingosine‐1‐phosphate receptor type 1 regulates glioma cell proliferation and correlates with patient survival

Sphingosine‐1‐phosphate plays a role in the suppression of lateral pseudopod formation during Dictyostelium discoideum cell migration and chemotaxis

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