Folic acid inhibits endothelial cell migration through inhibiting the RhoA activity mediated by activating the folic acid receptor/cSrc/p190RhoGAP-signaling pathway

Hou, Tien Chi; Lin, Jheng Jhe; Wen, Heng Ching; Chen, Li Ching; Hsu, Sung Po; Lee, Wen Sen

doi:10.1016/j.bcp.2012.11.011

Cited by 29 publications

(28 citation statements)

References 25 publications

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“…In line with this study, folic acid prevented the ethanol-induced RhoGDI and gelsolin depletion, thus positively modulating Rho-dependent actin motility (63). Of note, a recent report demonstrated a different mode of interaction of folic acid with Rho pathways through the effect of the folate receptor on c-Src/RhoGDI (64). This mechanism, which is downstream of GTPase post-translational modification, inhibited RhoA and associated cellular migration.…”

Section: Discussionsupporting

confidence: 83%

Rho GTPases RhoA and Rac1 Mediate Effects of Dietary Folate on Metastatic Potential of A549 Cancer Cells through the Control of Cofilin Phosphorylation

Oleinik

Helke

Kistner-Griffin

et al. 2014

Journal of Biological Chemistry

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Background: Molecular mechanisms translating effects of folate on metastasis are not clear. Results: Folate restriction inhibits methylation and membrane translocation of Rho GTPases in A549 cancer cells and provides survival advantage in mice with lung cancer. Conclusion: Folate enhances migratory ability and invasiveness of cancer cells through Rho GTPase pathways and promotes metastasis. Significance: This study highlights the interaction between nutrients and metastasis-related signaling.

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Section: Discussionsupporting

confidence: 83%

Rho GTPases RhoA and Rac1 Mediate Effects of Dietary Folate on Metastatic Potential of A549 Cancer Cells through the Control of Cofilin Phosphorylation

Oleinik

Helke

Kistner-Griffin

et al. 2014

Journal of Biological Chemistry

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“…With a variety of biological functions, RhoA plays an important role in the regulation of the actin cytoskeleton, which is mainly involved in the reorganization of the cytoskeleton, cell migration and adhesion, cell polarization and activation and DNA transcription, as well as other functions (30,31). In the reproductive field, Melendez et al found that RhoA was essential in mouse embryonic fibroblastic mitosis (9).…”

Section: Discussionmentioning

confidence: 99%

The PI3K/Akt signaling pathway exerts effects on the implantation of mouse embryos by regulating the expression of RhoA

Liu

Wang

2014

International Journal of Molecular Medicine

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The aim of this study was to investigate whether the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway affects the implantation of mouse embryos by regulating the expression of RhoA. The expression of PI3K, Akt, phosphorylated (p-)Akt, phosphatase and tensin homolog (PTEN) and RhoA in the uterus of mice on day 5 of pregnancy (D5) and in pseudopregnant mice was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry and western blot analysis. A functional analysis of these genes was also performed by the intrauterine injection with the PI3K inhibitor, LY294002, on day 2 of pregnancy (D2). The expression levels of PI3K, p-Akt, RhoA at the implantation site were higher than those at the inter-implantation site in the endometrium; however, opposite effects were observed for PTEN expression. The expression levels of the above genes in the pseudopregnant group and in the group injected with the PI3K/Akt inhibitor, LY294002, were markedly lower than those in the pregnant group. Functional experiments revealed that the number of implantation sites had been significantly decreased (P<0.05) following the intrauterine injection of the PI3K inhibitor, LY294002, on day 2 of gestation compared with the contralateral injection of phosphate-buffered saline (PBS). These results suggest that the PI3K/Akt signaling pathway affects embryo implantation by regulating the expression of RhoA.

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“…Surprisingly, these cells actively sprouted, even in the absence of VEGF stimulation. This highly robust sprouting could be explained by several factors, including a higher density of receptors for angiogenic factors such as neuropilin-1 (NRP1) [33,34], leading to a response to very low levels in the medium even in the absence of supplementation, or the upregulation of genes related to migration and motility, including RhoA and RhoB[35–37]. However, it should be noted that the VEGFR1 and VEGFR2 gene expression level on the sprouting cells was similar to the control endothelial cell population.…”

Section: Discussionmentioning

confidence: 99%

Endothelial cells expressing low levels of CD143 (ACE) exhibit enhanced sprouting and potency in relieving tissue ischemia

2014

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The sprouting of endothelial cells from pre-existing blood vessels represents a critical event in the angiogenesis cascade. However only a fraction of cultured or transplanted endothelial cells form new vessels. Moreover it is unclear if this results from a stochastic process or instead relates to certain endothelial cells having a greater angiogenic potential. This study investigated whether there exists a sub-population of cultured endothelial cells with enhanced angiogenic potency in vitro and in vivo. First, endothelial cells that participated in sprouting, and non-sprouting cells, were separately isolated from a 3D fibrin gel sprouting assay. Interestingly, the sprouting cells, when placed back into the same assay, displayed a 7-fold increase in the number of sprouts, as compared with control cells. Angiotensin converting enzyme (CD143) was significantly down regulated on sprouting cells, as compared to regular endothelial cells. A subset of endothelial cells with low CD143 expression was then prospectively isolated from an endothelial cell culture. Finally, these cells were found to have greater potency in alleviating local ischemia, and restoring regional blood perfusion when transplanted into ischemic hindlimbs, as compared with unsorted endothelial cells. In summary, this study indicates that low expression of CD143 can be used as a biomarker to identify an endothelial cell subpopulation that is more capable to drive neovascularization.

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Folic acid inhibits endothelial cell migration through inhibiting the RhoA activity mediated by activating the folic acid receptor/cSrc/p190RhoGAP-signaling pathway

Cited by 29 publications

References 25 publications

Rho GTPases RhoA and Rac1 Mediate Effects of Dietary Folate on Metastatic Potential of A549 Cancer Cells through the Control of Cofilin Phosphorylation

Rho GTPases RhoA and Rac1 Mediate Effects of Dietary Folate on Metastatic Potential of A549 Cancer Cells through the Control of Cofilin Phosphorylation

The PI3K/Akt signaling pathway exerts effects on the implantation of mouse embryos by regulating the expression of RhoA

Endothelial cells expressing low levels of CD143 (ACE) exhibit enhanced sprouting and potency in relieving tissue ischemia

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