SPIN1 promotes gastric cancer invasion and metastasis via Slug/claudin-1-induced epithelial-mesenchymal transition

Metastases are responsible for over 90% of the deaths in patients with gastric cancer (GC). Our previous study revealed that SPIN1 promotes the invasion and metastasis of GC; however, the underlying mechanism remains unclear. Transwell assays were used to assess cell migration and invasion ability. A mouse model of distant metastasis was established to investigate the regulatory role of SPIN1 in GC invasion and metastasis in vivo . RT-qPCR and western blotting were performed to assess the expression levels of EMT-related proteins. The expression of SPIN1, Slug, and claudin-1 was examined by IHC staining of tissue microarrays. Statistical analyses were performed to establish correlations between their expression levels and clinicopathological characteristics. SPIN1 promoted GC cell invasion and metastasis in vitro and in vivo . Overexpression of SPIN1 could lead to upregulation of Slug expression and downregulation of claudin-1 expression, whereas silencing of SPIN1 could lead to downregulation of Slug expression and upregulation of claudin-1. The expression levels of SPIN1 and Slug were significantly higher in GC tissues than in normal gastric mucosa. SPIN1 expression was positively correlated with Slug expression and negatively correlated with claudin-1 expression. GC patients with high SPIN1 and Slug expression were associated with higher TNM stage, more LN metastasis, distant metastasis, and worse overall survival. Overall, we elucidated the function of SPIN1 in GC and identified Slug/ claudin-1-mediated Epithelial-mesenchymal transition (EMT) as a novel mechanism by which SPIN1 contributes to migration and invasion of GC. Combined inhibition of SPIN1 and Slug may be a potential therapeutic approach to disrupt GC metastasis.