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Experimental evidence indicates a critical role of TRPV4 (Transient Receptor Potential Vanilloid 4) in controlling the cell migratory activity of multiple tumors. However, the oncogenic role of TRPV4 in glioma still remains elusive. In this study, we tried to investigate the oncogenic role of TRPV4 in glioma. We found that the expression levels of TRPV4 were upregulated in glioma and the high levels of TRPV4 indicated a worse prognosis in patients with glioma. TRPV4 was critical for glioma migration and invasion: activating TRPV4 by agonist GSK1016790 A enhanced glioma migration and invasion, while, the specific TRPV4 antagonist HC-067047 suppressed glioma migration and invasion. Mechanically, activated TRPV4 promoted the activation of Rac1 (Ras-related C3 botulinum toxin substrate 1) by targeting the AKT for phosphorylation, then enhanced glioma migration and invasion. All these results suggested that TRPV4 accelerates glioma migration and invasion through the AKT/Rac1 signaling, and TRPV4 might be considered as a potential target for glioma therapy.
This article was published in the following journal.
Name: Biochemical and biophysical research communications
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An SHC-signaling adaptor protein that transduces PHOSPHOTYROSINE-dependent signals downstream of RECEPTOR PROTEIN-TYROSINE KINASES and non-receptor tyrosine kinases. It is required for TGF-BETA-induced CELL MIGRATION; NEOLPASM INVASION; and METASTASIS of BREAST NEOPLASMS; its SH2 DOMAIN is essential for tumor survival. It also functions in signaling downstream of ANGIOPOIETIN RECEPTOR TIE-2, regulating the migration of ENDOTHELIAL CELLS; and PHYSIOLOGIC NEOVASCULARIZATION.
Specific assays that measure the migration of cells. They are commonly used to measure the migration of immune cells in response to stimuli and the inhibition of immune cell migration by immunosuppressive factors.
A Wnt protein and ligand for FRIZZLED RECEPTORS that may function as an inhibitor or activator of the WNT SIGNALING PATHWAY. For example, it activates signaling in the presence of Frizzled-4 but is inhibitory when coupled with ROR2 TYROSINE KINASE. It is required for axis formation during EMBRYOGENESIS and inhibits the proliferation, migration, and invasiveness of cancer cells.
A Rho guanine nucleotide exchange factor that consists of two pleckstrin homology domains flanking central Ras-binding, Dbl-homology (DH) and PDZ domains. It stimulates GTP-GDP exchange of rho-like GTPases such as RAC1 PROTEIN; CDC42 PROTEIN; and RHOA PROTEIN, and functions to link extracellular signals to remodeling of the CYTOSKELETON for CELL ADHESION and CELL MOVEMENT.
Protein factor(s) released by sensitized lymphocytes (and possibly other cells) that inhibit the movement of LEUKOCYTES, especially polymorphonuclear cells, away from their site of release. Assays for these factors are used as tests for cellular immunity. Two of the common assays are the LEUKOCYTE MIGRATION CAPILLARY TUBE TECHNIQUE (LMCT) and the LEUKOCYTE MIGRATION AGAROSE TEST (LMAT).