IGF1/IGF1R/STAT3 signaling-inducible IFITM2 promotes gastric cancer growth and metastasis

Abstract

Interferon-induced transmembrane proteins (IFITMs) are expressed in some types of cancer. However, their precise roles in tumor progression remain unclear. The present study investigated the function of IFITM2 in gastric cancer (GC) progression. A retrospective analysis of a public database and 167 GC patients revealed that IFITM2 expression was upregulated in gastric tumor samples, which was positively correlated with disease progression, more frequent postoperative recurrence, and higher mortality rate. IFITM2 knockdown decreased GC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition in vitro. We also found that IFITM2 expression was in part induced by insulin-like growth factor (IGF) 1 via IGF1 receptor/signal transducer and activator of transcription 3 signaling. Furthermore, IFITM2 regulated interleukin-6 expression and secretion, which in turn increased IFITM2 expression. Silencing of IFITM2 expression suppressed tumor growth and lung metastasis in vivo. These results suggest that IFITM2 is a novel prognostic biomarker and regulator of GC progression.

Keywords: EMT; Gastric cancer; IGF1/IGF1R/STAT3; IL-6; Interferon-induced transmembrane protein 2.