Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in intestinal type gastric cancer

Abstract

Smad interacting protein 1 (SIP1) is an epithelial-mesenchymal transition (EMT)-inducible gene that plays a key role in tumor progression in various cancers. This study seeks to clarify the clinical and biological significance of SIP1 expression, especially in intestinal type gastric cancer. We analyzed the mRNA levels of SIP1 and other EMT regulators by real-time reverse transcription PCR in gastric tissue samples of 134 gastric cancer patients, and in five gastric cancer cell lines. SIP1 gene knockdown by siRNA transfection was performed to evaluate SIP1 function in gastric cancer cells. Expression of the SIP1 gene was significantly higher in cancerous tissue than in adjacent normal mucosa. Although the mRNA expression of the other EMT regulators tested (Snail, Slug, and Twist) was not correlated with clinicopathological factors, increased SIP1 expression was an independent prognostic factor and an independent risk factor for peritoneal dissemination. In addition, SIP1 expression was significantly positive and correlated with vimentin expression. For intestinal type gastric cancer in particular, elevated SIP1 expression was significantly correlated with peritoneal dissemination and poor prognosis (p<0.05). In vitro, cell proliferation, migration, invasion, and resistance to anoikis were significantly inhibited in SIP1 siRNA-transfected MKN7 cells compared to control siRNA. SIP1 appears to play an important role in progression to peritoneal carcinomatosis and may be a therapeutic target for patients with intestinal type gastric cancer.