Abrogation of galectin-4 expression promotes tumorigenesis in colorectal cancer.

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.

• Authors: Seung Won Kim, Ki Cheong Park, Soung Min Jeon, Tak Bum Ohn, Tae Il Kim, Won Ho Kim, Jae Hee Cheon
• Journal: Cellular oncology (Dordrecht) (Cell Oncol (Dordr)) Vol. 36 Issue 2 Pg. 169-78 (Apr 2013) ISSN: 2211-3436 [Electronic] Netherlands
• PMID: 23378274 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Animals
• Blotting, Western
• Cell Proliferation
• Cell Transformation, Neoplastic (genetics, metabolism, pathology)
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Cyclooxygenase 2 (metabolism)
• Galectin 4 (genetics, 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