Abstract: Background and purpose: Stanniocalcin 1 (STC1) is associated with the development of cancer and poor prognosis. However, the effect of STC1 on lung cancer cell metastasis and its mechanism have not yet been fully clarified. The purpose of this study was to investigate the effect of STC1 on invasion and migration of lung cancer cells and its possible molecular mechanisms. Methods: HLEC-STC1 cell line overexpressing STC1 with the control cell line HLEC-EV and A549-STC1 siRNA cell line silencing STC1 with the control cell line A549-EV were constructed. Transwell and scratch assays were used to detect cell invasion and migration abilities. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot were used to detect the changes of mRNA and protein levels of epithelial-mesenchymal transition (EMT) markers. Cellular immunofluorescence technique was used to further verify the expression and localization of EMT markers. Western blot was used to detect EMT-related signaling pathway proteins and the levels of transcription factors. Results: Compared with the control cells, the invasion and migration abilities of HLEC-STC1 cells overexpressing STC1 were enhanced, while the invasion and migration abilities of STC1-silencing A549-STC1 siRNA cells were weakened (P<0.05).In HLEC-STC1 cells overexpressing STC1,the expression of E-cadherin was down-regulated, while the expression levels of N-cadherin, vimentin and epithelial cell adhesion molecule (EpCAM) were up-regulated (P<0.05). The expression of E-cadherin was up-regulated in A549-STC1 siRNA cells with low expression of STC1. The expression levels of N-cadherin, vimentin and EpCAM were down-regulated (P<0.05). Meanwhile, the expression levels of extracellular signal-regulated protein kinase (ERK) and Wnt/β-catenin signaling pathways in HLEC-STC1 cells were increased, and the expression of transcription factor ZEB1 was elevated. The expression level of Snail1 was up-regulated, and the results were opposite in A549-STC1 siRNA cells (P<0.05). Conclusion: STC1 may up-regulate the expression levels of transcription factors ZEB1 and Snail1 by activating ERK and Wnt/β-catenin signaling pathways, thereby inducing EMT to promote invasion and migration of lung cancer cells.

Key words: Stanniocalcin 1, Lung cancer cells, Epithelial-mesenchymal transition, Invasion, Migration