Galectin-1 induces gastric cancer stem cell population through the activation of Wnt/β-Catenin Signaling

Abstract

Galectin-1 is a proto-type of lectin that has one carbohydrate recognition domain and it has high affinity for β-galactosides. The different expressions of galectin-1 in normal and tumor tissues of various cancers and the functions of galectin-1 have been documented in several articles. They introduced the intracellular and extracellular role of galectin-1 through the regulation of immune response, tumor progression and metastasis. In gastric cancer, it was reported that the expression level of galectin-1 is higher in malignant tissues than normal tissues of gastric cancer patients, however, the role of galectin-1 is not elucidated, yet. In this study, we demonstrated that galectin-1 regulates Wnt/β-catenin signaling pathway to induce the number of gastric cancer stem cell population, suggesting that galectin-1 could be a target molecule for gastric cancer therapy. We conformed that the expression level of galectin-1 is highly expressed in tumor tissues of gastric cancer patients and its expression is reversely correlated to survival probability and first progression rate. Depletion of galectin-1 by its specific siRNAs decreased the cell proliferation, migration, invasion and sphere forming ability of gastric cancer AGS, YCC-2 and SNU-668 cells. On the contrary, over-expression of galectin-1 increased the cell proliferation, migration, invasion and sphere forming ability. We also performed the colony forming assay and Hoechst 33342 dye exclusion assay using gastric cancer MKN-28 cells, and determined that depletion of galectin-1 reduced the side population of gastric cancer cells. These results suggest that galectin-1 increases the stemness property of gastric cancer cells. To determine the mechanism, we demonstrated which pathway is regulated by galectin-1 in gastric cancer cells. Interestingly, TOP-Flash luciferase activity, which represents the activation of Wnt/β-catenin signaling, was significantly regulated by galectin-1 without β-catenin transcriptional regulation and nuclear accumulation. Take these together, galectin-1 regulates Wnt/β-catenin signaling and then increases the stemness property of gastric cancer cells. We suppose here that galectin-1 could be a target molecule to do diagnosis and therapy of gastric cancer.