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

Cancer Sci. 2016 Oct;107(10):1390-1398. doi: 10.1111/cas.13016. Epub 2016 Sep 4.

Abstract

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.

Keywords: Galectin-1; JNK; invasion; shRNA; urothelial bladder urinary carcinoma.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival / genetics
  • Galectin 1 / genetics
  • Galectin 1 / metabolism*
  • Gene Expression
  • Gene Knockdown Techniques
  • Gene Silencing
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MAP Kinase Signaling System*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Galectin 1
  • RNA, Small Interfering
  • JNK Mitogen-Activated Protein Kinases