Apolipoprotein C1 regulates gastric cancer progression by inducing epithelial-mesenchymal transition via the JAK/STAT pathway

Abstract

Abstract This study aimed to determine the role of apolipoprotein C1 (APOC1) in GC (gastric cancer), as well as elucidate the mechanism of its effects. We studied the relationship between clinicopathological characteristics and APOC1 expression in 127 patients with GC, and determined the effects of APOC1 on GC cell apoptosis, proliferation, migration, invasion, and metastasis. We analyzed markers of epithelial-mesenchymal transition (EMT) and JAK/STAT signaling protein expression, and determined the effects of the STAT3 activator colivelin on APOC1-knockdown GC cells. High APOC1 expression was observed in GC tissues and cells; the level correlated with GC differentiation degree, T stage, and TNM stage. There was an association between high APOC1 expression and poor prognosis. APOC1 knockdown induced GC cell apoptosis and inhibited EMT, migration, invasion, and proliferation in vitro, besides reduced the weight and volume of subcutaneous xenotransplanted tumors and the number of hepatic metastatic foci in vivo in a mouse model. APOC1 knockdown caused inhibition of phosphorylated-STAT3 protein expression, upregulation of E-cadherin, and downregulation of N-cadherin and vimentin in GC cells; these effects were reversed by JAK/STAT reactivation. Thus, APOC1 participates in EMT and regulates apoptosis, invasion, migration, as well as metastasis of gastric cancer via the JAK1/STAT3 pathway.