DcR3 induces proliferation, migration, invasion, and EMT in gastric cancer cells via the PI3K/AKT/GSK-3β/β-catenin signaling pathway

Abstract

BackgroundDecoy receptor 3 (DcR3) has been reported to be overexpressed in a wide variety of malignancies and is correlated with tumorigenesis and progression. In gastric cancer (GC), DcR3 overexpression is associated with lymph node and distant metastasis, as well as poor prognosis. However, the functional role of DcR3 expression in GC remains elusive.PurposeThe aim of this study is to elucidate the direct role of DcR3 in regulating GC progression and metastasis and identify the potential mechanism.MethodsDcR3 expression was stably knocked down in HGC27 and MKN28 cells by transfecting the cells with DcR3 shRNA using lentiviral vector system. After the knockdown of DcR3 was confirmed, cell proliferation, colony formation, cell cycle distribution, apoptosis, cell invasion and migration were assessed in vitro. In addition, Western blot analysis was performed to evaluate the expression of downstream mediators of DcR3. Comparisons between multiple groups were performed using one-way analysis of variance (ANOVA) or unpaired Student’s t-test. Differences were considered significant at P<0.05.ResultsOur findings demonstrate that DcR3 induces proliferation, migration, invasion, and promotes epithelial-mesenchymal transition (EMT) of GC cells. In addition, DcR3 increases the expression levels of several components of the PI3K/AKT/GSK-3β/β-catenin signaling pathway, such as p-AKT, GSK-3β, p-GSK-3β and β-catenin. Additionally, DcR3 also enhances the expression of N-cadherin and Vimentin and decreases the expression of E-cadherin.ConclusionIn summary, the findings of this study indicate that during GC progression, DcR3 plays a key role in cell proliferation and invasion via the PI3K/AKT/GSK-3β/β-catenin signaling pathway. Thus, targeting DcR3 might be a potential therapeutic approach for the treatment of GC.

Fatty acid oxidation inhibitor etomoxir suppresses tumor progression and induces cell cycle arrest via PPARγ-mediated pathway in bladder cancer

“…Moreover, we observed an inhibitory effect of etomoxir on invasion and migration, with down-regulated N-cadherin and up-regulated E-cadherin proteins related to EMT, which have been certified to have a critical role in cancer cell invasion and migration [42]. The phosphorylation of AKT at Ser 9 could regulate the EMT pathway [43], which was consistent with our WB results of down-regulated phosphorylated/total AKT ( Figure 4F and Supplementary Figure S2E). Furthermore, accumulating studies reported that FAO activation was an important mechanism for tumor cells to develop drug resistance [44].…”

PPARγ inhibition regulates the cell cycle, proliferation and motility of bladder cancer cells

“…53 Consistently, in this study, the potential BCa marker vimentin was reduced in BCa T24 cells treated with PPARγ deficiency. 54 Consistently, in our study, we noted that phosphorylated/total AKT was down-regulated and phosphorylated/total GSK3β was up-regulated, which indicated that the alteration of EMT might be regulated via the AKT/GSK3β signalling pathway. 54 Consistently, in our study, we noted that phosphorylated/total AKT was down-regulated and phosphorylated/total GSK3β was up-regulated, which indicated that the alteration of EMT might be regulated via the AKT/GSK3β signalling pathway.…”

“…The phosphorylation of AKT at Ser9 could inhibit the activity of GSK-3β. 54 Consistently, in our study, we noted that phosphorylated/total AKT was down-regulated and phosphorylated/total GSK3β was up-regulated, which indicated that the alteration of EMT might be regulated via the AKT/GSK3β signalling pathway.…”

高表达lncRNA FOXD2-AS1促进非小细胞肺癌的上皮-间充质转化

“…EMT is of complex mechanism and plays an important role in pathological process including invasion and migration of neoplasms (38). To further explore the potential mechanisms of FOXD2-AS1 in NSCLC, we examined the effects of FOXD2-AS1 on EMT markers: CK18, E-cadherin, α-SMA, and FN.…”

“…advbiomed.0003.2019Advances in biology and medicine, 2019,Vol.4(No.1),pp:[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] …”