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Abrogation of galectin-4 expression promotes tumorigenesis in colorectal cancer

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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.

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Acknowledgments

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (grant number 2009-0069149) and a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (grant number A120176). We would like to thank the tissue donors for their contribution to this study.

Conflict of interest

The authors have declared that no conflict of interest exists.

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Author notes

  1. Soung Min Jeon

    Present address: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Dankook University College of Medicine, Chungcheongnam-do, Korea

Authors and Affiliations

  1. Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea

    Seung Won Kim, Soung Min Jeon, Tae Il Kim, Won Ho Kim & Jae Hee Cheon

  2. Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, Korea

    Seung Won Kim, Ki Cheong Park, Won Ho Kim & Jae Hee Cheon

  3. Department of Surgery, Yonsei University College of Medicine, Seoul, Korea

    Ki Cheong Park

  4. Division of Natural Medical Sciences, Chosun University, Gwangju, Korea

    Tak Bum Ohn

  5. Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea

    Jae Hee Cheon

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Kim, S.W., Park, K.C., Jeon, S.M. et al. Abrogation of galectin-4 expression promotes tumorigenesis in colorectal cancer. Cell Oncol. 36, 169–178 (2013). https://doi.org/10.1007/s13402-013-0124-x

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