The antagonistic roles of PDGF and integrin αvβ3 in regulating ROS production at focal adhesions

Lin, Li-Jung; Grimme, Jill M.; Sun, Jie; Lu, Shaoying; Gai, Lisa; Wang, Yingxiao

doi:10.1016/j.biomaterials.2013.01.092

Cited by 19 publications

(18 citation statements)

References 47 publications

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“…FA‐dependent production of ROS after response to growth factors (a Rac1‐dependent process) is limited by an α V β 3 /RhoA stimulation after adhesion on fibronectin (51). In line with these regulations, we can speculate that the reduction of FA along with the diminution of fibronectin deposition (as presented in this report) is associated with reduced α V β 3 /RhoA signaling.…”

Section: Discussionmentioning

confidence: 99%

Rac1 GTPase silencing counteracts microgravity‐induced effects on osteoblastic cells

et al. 2014

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Bone cells exposed to real microgravity display alterations of their cytoskeleton and focal adhesions, two major mechanosensitive structures. These structures are controlled by small GTPases of the Ras homology (Rho) family. We investigated the effects of RhoA, Rac1, and Cdc42 modulation of osteoblastic cells under microgravity conditions. Human MG-63 osteoblastlike cells silenced for RhoGTPases were cultured in the automated Biobox bioreactor (European Space Agency) aboard the Foton M3 satellite and compared to replicate ground-based controls. The cells were fixed after 69 h of microgravity exposure for postflight analysis of focal contacts, F-actin polymerization, vascular endothelial growth factor (VEGF) expression, and matrix targeting. We found that RhoA silencing did not affect sensitivity to microgravity but that Rac1 and, to a lesser extent, Cdc42 abrogation was particularly efficient in counteracting the spaceflight-related reduction of the number of focal contacts [؊50% in silenced, scrambled (SiScr) controls vs. ؊15% for SiRac1], the number of F-actin fibers (؊60% in SiScr controls vs. ؊10% for SiRac1), and the depletion of matrix-bound VEGF (؊40% in SiScr controls vs. ؊8% for SiRac1). Collectively, these data point out the role of the VEGF/Rho GTPase axis in mechanosensing and validate Rac1-mediated signaling pathways as potential targets for counteracting microgravity effects.-Guignandon, A., Faure, C., Neutelings, T., Rattner, A., Mineur, P., Linossier, M.-T., Laroche, N., Lambert, C., Deroanne, C., Nusgens, B., Demets, R., Colige, A., Vico, L. Rac1 GTPase silencing counteracts microgravityinduced effects on osteoblastic cells. FASEB J. 28, 4077-4087 (2014). www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Rac1 GTPase silencing counteracts microgravity‐induced effects on osteoblastic cells

et al. 2014

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“…Recently, these data have been corroborated by live cell imaging of fibroblasts, in which a fluorescent redox probe was directed to focal adhesions via a paxillin tag. Thereby, it was demonstrated that a plateletderived growth factor (PDGF)-elicited ROS signal is reduced in aVb3 integrin-containing focal adhesions of fibroblasts attached onto fibronectin (94). Leukocytes are also well-known for their capacity to release substantial amounts of ROS, especially in the respiratory burst, while they attack pathogens (28,125).…”

Section: Eble and De Rezendementioning

confidence: 99%

Redox-Relevant Aspects of the Extracellular Matrix and Its Cellular ContactsviaIntegrins

EbleJohannes

Figueiredo

2014

Antioxidants & Redox Signaling

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“…Some ROS-regulated proteins were identified to play key roles in epithelial-mesenchymal transition and tumor metastasis. Integrin family members are of those ROS-regulated proteins [ 13 , 14 ]. Integrins are heterodimeric cell surface glycoproteins consisting of α and β subunits and control the attachment of cells to the extracellular matrix (ECM).…”

Section: Introductionmentioning

confidence: 99%

Involvement of ROS-alpha v beta 3 integrin-FAK/Pyk2 in the inhibitory effect of melatonin on U251 glioma cell migration and invasion under hypoxia

Wang

Huang

et al. 2015

J Transl Med

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BackgroundMelatonin, a well-known antioxidant, has been shown to possess anti-invasive properties for glioma. However, little is known about the effect of melatonin on glioma cell migration and invasion under hypoxia, which is a crucial microenvironment for tumor progress. In addition, focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) are closely associated with cell migration and invasion. Therefore, we investigated the possible role of these kinases and its related signaling in the regulation of human U251 glioma cells behavior by melatonin under hypoxia.MethodsThe abilities of migration and invasion of U251 glioma cells were determined by wound healing and transwell assay in vitro. The intracellular production of reactive oxygen species (ROS) was measured by using the fluorescent probe 6-carboxy-2′, 7′-dichorodihydrofluorescein diacetate (DCFH-DA). Immunofluorescence experiments and western blotting analysis were used to detect the expression level of protein. Small interfering RNAs (siRNA) was used to silence specific gene expression.ResultsThe pharmacologic concentration (1 mM) of melatonin significantly inhibited the migration and invasion of human U251 glioma cells under hypoxia. The inhibitory effect of melatonin was accompanied with the reduced phosphorylation of FAK and Pyk2, and decreased expression of alpha v beta 3 (αvβ3) integrin. Additionally, inhibition of αvβ3 integrin by siRNA reduced the phosphorylation of FAK/Pyk2 and demonstrated the similar anti-tumor effects as melatonin, suggesting the involvement of αvβ3 integrin- FAK/Pyk2 pathway in the anti-migratory and anti-invasive effect of melatonin. It was also found that melatonin treatment decreased the ROS levels in U251 glioma cells cultured under hypoxia. ROS inhibitor apocynin not only inhibited αvβ3 integrin expression and the phosphorylation levels of FAK and Pyk2, but also suppressed the migratory and invasive capacity of U251 glioma cells under hypoxia.ConclusionsThese results suggest that melatonin exerts anti-migratory and anti-invasive effects on glioma cells in response to hypoxia via ROS-αvβ3 integrin-FAK/Pyk2 signaling pathways. This provides evidence that melatonin may be a potential therapeutic molecule targeting the hypoxic microenvironment of glioma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0454-8) contains supplementary material, which is available to authorized users.

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The antagonistic roles of PDGF and integrin αvβ3 in regulating ROS production at focal adhesions

Cited by 19 publications

References 47 publications

Rac1 GTPase silencing counteracts microgravity‐induced effects on osteoblastic cells

Rac1 GTPase silencing counteracts microgravity‐induced effects on osteoblastic cells

Redox-Relevant Aspects of the Extracellular Matrix and Its Cellular ContactsviaIntegrins

Involvement of ROS-alpha v beta 3 integrin-FAK/Pyk2 in the inhibitory effect of melatonin on U251 glioma cell migration and invasion under hypoxia

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