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C2GnT-M is downregulated in colorectal cancer and its re-expression causes growth inhibition of colon cancer cells

Oncogene volume 25, pages 3267–3276 (2006)Cite this article

Abstract

Changes in carbohydrates on the cell surface are associated with tumor malignancy. The mucin-type core 2 β-1,6-N-acetylglucosaminyltransferase (C2GnT-M) is highly expressed in the gastrointestinal tract and catalyses the formation of core 2, core 4, and blood group I branches on O-glycans. In the present study, we evaluated the role of C2GnT-M in colorectal cancer. C2GnT-M downexpression was observed in 73.6% of the primary tumors from colorectal cancer patients (39 of 53) analysed by cancer profiling array. Consistently, the majority of colon cancer cell lines and primary colon tumors expressed lower levels of C2GnT-M than did normal colon tissues by RT–PCR. HCT116 cells stably transfected with C2GnT-M inhibited expression of the core 1 structure, Galβ1,3GalNAcα1-Ser/Thr, on the cell surface. Moreover, C2GnT-M expression suppressed cell adhesion, motility, and invasion as well as colony formation ability. The growth of C2GnT-M-transfected HCT116 and SW480 cells was dramatically suppressed, and the cell death induced by C2GnT-M was demonstrated by an increase in the annexin V-positive cells. Interestingly, C2GnT-M inhibited cell adhesion to collagen IV and fibronectin, and decreased tyrosine phosphorylation of paxillin, indicating that the changes in cancer behavior may be partly mediated by integrin-signaling pathways. Tumor growth in vivo was also significantly suppressed by C2GnT-M in the xenografts of nude mice. These results demonstrate that C2GnT-M is frequently downregulated in colorectal cancer and suppresses colon cancer cell growth.

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Abbreviations

RT–PCR:

reverse –transcription–polymerase chain reaction

C2GnT:

core 2 β-1,6-N-acetylglucosaminyltransferase

C4GnT:

core 4 β-1,6-N-acetylglucosaminyltransferase

FAK:

focal adhesion kinase

ST6GalNAc I:

CMP, sialic acid:Gal β1,3GalNAc-R α6-sialyltransferase I

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Acknowledgements

We thank Dr Fang-Jen S Lee for cancer profiling array analysis, Drs Tsai-Kun Li and Shu-Chun Teng for support and help, Dr Tzuu-Shuh Jou for anti-myc mAb, Dr Jih-Hwa Guh for HT29 cell line, Dr Shyh-Chyi Lo for anti-I polyclonal antibody, and Ru-Ying Tsai for technical assistance. This study was supported by National Health Research Institute Grant NHRI-EX94-9410BC; National Science Council Grants NSC 92-2321-B-002-024 and NSC93-2320-B-002-126, and National Taiwan University Hospital Grants NTUH.92A16, NTUH.93A03 and NTUH.094M13.

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Author notes

  1. H-Y Chen and H-C Huang: These two authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Anatomy & Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan

    M-C Huang, H-Y Chen & N-Y Lin

  2. Animal Research Institute, Miaoli, Taiwan

    H-C Huang

  3. Department of Surgery, National Taiwan University College of Medicine, Taipei, Taiwan

    J Huang & J-T Liang

  4. Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan

    T-L Shen

  5. Department of Internal medicine, National Taiwan University Hospital, Taipei, Taiwan

    C-C Ho

  6. Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

    I-M Cho

  7. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan

    S-M Hsu

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Correspondence to M-C Huang.

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Huang, MC., Chen, HY., Huang, HC. et al. C2GnT-M is downregulated in colorectal cancer and its re-expression causes growth inhibition of colon cancer cells. Oncogene 25, 3267–3276 (2006). https://doi.org/10.1038/sj.onc.1209350

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