Abrogation of galectin-4 expression promotes tumorigenesis in colorectal cancer

Cell Oncol (Dordr). 2013 Apr;36(2):169-78. doi: 10.1007/s13402-013-0124-x. Epub 2013 Feb 2.

Abstract

Background: Although it has been well established that galectin-4 is selectively expressed by intestinal epithelial cells, the role of galectin-4 in colorectal cancer (CRC) development is, as yet, poorly understood. Here, we aimed to explore the role of galectin-4 in CRC development, both in vitro and in vivo.

Methods: Galectin-4 expression was investigated in tissue specimens from patients with adenoma, carcinoma and ulcerative colitis (UC) using immunohistochemistry. Colorectal cancer-derived HT-29 cells, in which galectin-4 expression was knocked down, were established using shRNA. mRNA and protein expression levels of galectin-4 and several downstream cancer-related genes were analyzed using RT-PCR, qPCR array, Western blotting, and immunofluorescence assays. To investigate the effect of galectin-4 expression abrogation on tumorigenesis in vivo, xenograft assays were performed.

Results: Immunohistochemistry analyses showed high expression levels of galectin-4 in normal colon mucosa tissues. Conversely, the expression levels of galectin-4 were significantly lower in CRC samples and its precursor lesions with dysplasia or inflammation. We found that shRNA-mediated galectin-4 silencing increases cell proliferation and, concomitantly, activates NF-κB and STAT3 signaling along with IL-6 up-regulation. In addition, we found that shRNA-mediated galectin-4 silencing promotes the expression of NF-κB target genes and other cancer-related genes and, concomitantly, enhances the in vivo growth of xenografts.

Conclusions: We show that abrogation of galectin-4 expression promotes cancer cell proliferation and, for the first time, provide evidence that down-regulation of galectin-4 elicits tumor promotion in vitro and in vivo through activation of IL-6/NF-κB/STAT3 signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Cyclooxygenase 2 / metabolism
  • Galectin 4 / genetics*
  • Galectin 4 / metabolism
  • Gene Expression Regulation, Neoplastic
  • HT29 Cells
  • Humans
  • Immunohistochemistry
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Nude
  • NF-kappa B / metabolism
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Transplantation, Heterologous
  • Tumor Burden

Substances

  • Galectin 4
  • Interleukin-6
  • NF-kappa B
  • STAT3 Transcription Factor
  • Cyclooxygenase 2
  • PTGS2 protein, human