SALL4 Regulates TGF-?1 To Promote Gastric Cancer Metastasis And Its Mechanism

Objective:To explore the functional roles and molecular mechanisms of SALL4(spalt-like transcription factor 4)in gastric cancer growth and metastasis.To provide evidence for the regulation of epithelial-mesenchymal transition(EMT)by SALL4 through TGF-? signaling pathway,offering new molecular target for gastric cancer diagnosis and therapy.Methods:SALL4 shRNA and SALL4 overexpressing plasmid were used to trasfect human gastric cancer cells MGC-803 and HGC-27.Cell colony formation assay was used to evaluate the cell proliferation ability.To assess the cell motility wound healing assay was used.Cell migration and invasion ability were determined by using Transwell migration and Matrigel invasion assays.Quantitative real-time PCR and western blot were used to detect the expression of genes and proteins involved in EMT.Microarray and qRT-PCR were used to identify the target genes of SALL4.Rescue experiment was used to determine whether SALL4 exerts the above-mentioned effects through the regulation of TGF-? signaling pathway.Results: Cell growth,migration,and invasion abilities were reduced in MGC803 cells transfected with SALL4 shRNA.SALL4 knockdown increased the expression level of E-cadherin while decreased that of N-cadherin,vimentin,slug and twist in MGC803 cells.TGF-?1 expression level and SMAD2/3 phosphorylation were decreased when SALL4 was knocked down in MGC803 cells.SALL4 overexpression had the opposite effects in HGC-27 cells.In rescue experiment,TGF-?1 knockdown inhibited the promoting role of SALL4 in cell migration and invasion as well as EMT in gastric cancer cells.Conclusions:SALL4 promote the metastatic potential of gastric cancer cells.TGF-?1 is a key mediator of the oncogenic role of SALL4 in gastric cancer.