STAT3 promotes peritoneal metastasis of gastric cancer by enhancing mesothelial-mesenchymal transition.

Abstract

Signal transducer and activator of transcription 3 (STAT3) is a widely-reported oncogene in many human cancers, but its role in the peritoneal metastasis of gastric cancer (GC) has yet to be studied. The expression level of STAT3 in GC patient tissues was assessed. Stable shRNA knockdown (KD) of STAT3 was established in GCcell line AGS, followed by examination of its effect on AGC cell viability and proliferation, xenograft tumor growth, metastatic potential, mesothelial-to-mesenchymal transition (MMT)-related properties and peritoneal metastasis in a mouse model. The specific STAT3 inhibitor BP1-102 was also employed to verify findings from STAT3 KD experiments. Expression of activated STAT3 was upregulated in GC patient tumor tissues, and further elevated among patients diagnosed with peritoneal metastasis. STAT3 deactivation suppressed viability and proliferation of GCcells in vitro, as well as GC tumorigenesis in vivo. Furthermore, the metastatic properties and production of MMT-inducing factors of GC cells in vitro were also dependent on STAT3 activation. Importantly, STAT3 KD significantly compromised peritoneal metastasis of GC in vivo. STAT3 activation contributes to peritoneal metastasis of GC by promoting MMT, warranting further investigation to explore its potential for GC treatment, in particular among peritoneal metastasis patients.