Galectin-1 induces invasion and the epithelial-mesenchymal transition in human gastric cancer cells via non-canonical activation of the hedgehog signaling pathway

Abstract

// Yang Chong 1 , Dong Tang 1 , Jun Gao 1 , Xuetong Jiang 1 , Chuanqi Xu 1 , Qingquan Xiong 1 , Yuqin Huang 1 , Jie Wang 1 , Huaicheng Zhou 1 , Youquan Shi 1 , Daorong Wang 1 1 Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University, Subei People’s Hospital of Jiangsu Province, Yangzhou 225001, China Correspondence to: Daorong Wang, email: daorong666@sina.com Keywords: galectin-1, epithelial-mesenchymal transition, hedgehog signaling, Gli-1, gastric cancer Received: May 20, 2016      Accepted: October 21, 2016      Published: November 08, 2016 ABSTRACT Galectin-1 (Gal-1) has been reported to be an independent prognostic indicator of poor survival in gastric cancer and overexpression of Gal-1 enhances the invasiveness of gastric cancer cells. However, the downstream mechanisms by which Gal-1 promotes invasion remains unclear. Moreover, the function of Gal-1 in the epithelial-mesenchymal transition (EMT) in gastric cancer has not yet been elucidated. In this study, we observed Gal-1 expression was upregulated and positively associated with metastasis and EMT markers in 162 human gastric cancer tissue specimens. In vitro studies showed Gal-1 induced invasion, the EMT phenotype and activated the non-canonical hedgehog (Hh) pathway in gastric cancer cell lines. Furthermore, our data revealed that Gal-1 modulated the non-canonical Hh pathway by increasing the transcription of glioma-associated oncogene-1 ( Gli-1 ) via a Smoothened (SMO)-independent manner, and that upregulation of Gal-1 was strongly associated with gastric cancer metastasis. We conclude that Gal-1 promotes invasion and the EMT in gastric cancer cells via activation of the non-canonical Hh pathway, suggesting Gal-1 could represent a promising therapeutic target for the prevention and treatment of gastric cancer metastasis.