SLC6A8 is involved in the progression of non-small cell lung cancer through the Notch signaling pathway

BackgroundSolute carrier family 6 member 8 (SLC6A8) is known to be involved in the development of human tumors; however, the effect of SLC6A8 on the growth of non-small cell lung cancer (NSCLC) remains unclear. Here, we explored the role and potential action mechanism of SLC6A8 in NSCLC.MethodsWe used public databases [Oncomine, Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA)] to explore the expression of SLC6A8 in NSCLC. Additionally, we used immunohistochemistry to detect the expression of SLC6A8 in NSCLC clinicopathological tissues (cancer and adjacent tissues) and Western blotting to detect the expression of SLC6A8 in NSCLC clinicopathological tissues, NSCLC cell lines (A549, H1299, H520, and H1975), and a normal epithelial cell line (BEAS-2B). Using overexpression and knockdown of the SLC6A8 gene, we analyzed the in vitro effects of SLC6A8 on the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC and also the possible molecular mechanism with Notch signaling pathway.ResultsBioinformatic analysis demonstrated that SLC6A8 is highly expressed in NSCLC and is related to poor prognosis. We found that the expression of the SLC6A8 protein in human lung cancer tissues was significantly higher than that in adjacent tissues. In addition, it was also significantly higher in lung cancer cell lines (A549, H1299, H520, and H1975) than that in normal lung epithelium-BEAS-2B. Moreover, SLC6A8 overexpression promotes the proliferation, migration and invasion in vitro in NSCLC, accompanied by the activation of notch signaling pathway and the up-regulation of MMP9 and E-cadherin proteins. Knocking down SLC6A8 can inhibit the above effects on cells.ConclusionsSLC6A8 promotes the malignant progression of NSCLC and activates the Notch signaling pathway. Therefore, SLC6A8 is expected to become a molecular target for NSCLC treatment.