The results of the Cell Counting Kit-8 and invasion assays demonstrated that SPHK1 overexpression significantly enhanced the proliferation and invasion of a PTC cell line, consistent with clinical findings.
Downregulation of SPHK1 by lentiviral vector expressing SPHK1 small interfering (si)RNA evidently repressed Notch signaling and reduced the migration and invasion of thyroid carcinoma cells <i>in vitro</i> and in a NOD/SCID mouse model.
Sphingosine kinase 1 (SK1) is a lipid kinase whose activity produces sphingosine 1-phosphate, a prosurvival lipid associated with proliferation, angiogenesis, and invasion.
Moreover, EGFR and MEK1 inhibitors reduce both SK1 activation and cell invasion, suggesting that the enhanced invasiveness observed in the EGFR+ cells depends on the increased S1P secretion, downstream of the EGFRvIII-ERK-SK1-S1P pathway.
In addition, the inhibition of autophagy recovered CDH1 expression and reduced cell migration and invasion through delaying the degradation of CDH1 in SPHK1-overexpressing cells.
In conclusion, miR-124 inhibited cell proliferation and invasion in OS cells by downregulation of SPHK1, and that downregulation of SPHK1 was essential for the miR-124-inhibited cell invasion and in OS cells.
Knockout or pharmacological inhibition of SPHK1 in ovarian fibroblasts attenuated TGF-β-induced expression of CAF markers, and reduced their ability to promote ovarian cancer cell migration and invasion in a coculture system.
Taken together, our findings suggest that SphK1 can enhance the invasion and migration of NSCLC cells via activation of the AKT pathway and regulation of E-cadherin and Snail expression.
Furthermore, overexpression of SphK1 increased S1P levels, and the exogenous addition of S1P increased liver cell migration and invasion through the EDG1 receptor.
Sphingosine kinase 1 (SPHK1) is a newly discovered modulator of hypoxia inducible factor 1α (HIF-1α) with various biological activities such as cell growth, survival, invasion, angiogenesis, and carcinogenesis.