Role of galectin‐1 in urinary bladder urothelial carcinoma cell invasion through the JNK pathway

Human galectin‐1 is a member of the galectin family, proteins with conserved carbohydrate‐recognition domains that bind galactoside. Galectin‐1 is highly expressed in various tumors and participates in various oncogenic processes. However, detailed descriptions of the function of galectin‐1 in urinary bladder urothelial carcinoma have not been reported. Our previous cohort investigation showed that galectin‐1 is associated with tumor invasiveness and is a possible independent prognostic marker of urinary bladder urothelial carcinoma. The present study aimed to clarify the relevance of galectin‐1 expression level to tumor progression and invasion. In order to decipher a mechanism for the contribution of galectin‐1 to the malignant behavior of urinary bladder urothelial carcinoma, two bladder cancer cell lines (T24 and J82) were established with knockdown of galectin‐1 expression by shRNA. Bladder cancer cells with LGALS1 gene silencing showed reduced cell proliferation, lower invasive capability, and lower clonogenicity. Extensive signaling pathway studies indicated that galectin‐1 participated in bladder cancer cell invasion by mediating the activity of MMP9 through the Ras–Rac1–MEKK4–JNK–AP1 signaling pathway. Our functional analyses of galectin‐1 in urinary bladder urothelial carcinoma provided novel insights into the critical role of galectin‐1 in tumor progression and invasion. These results revealed that silencing the galectin‐1‐mediated MAPK signaling pathway presented a novel strategy for bladder cancer therapy.