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WTAP regulates migration and invasion of cholangiocarcinoma cells

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Wilms’ tumor 1-associating protein (WTAP) is a nuclear protein that has been associated with the regulation of proliferation and apoptosis. Although its dynamic expression and physiological functions in vascular cells have been reported, its expression and roles in cholangiocarcinoma cells are poorly characterized.

Methods

To examine the expression of WTAP in patient tissues, we performed immunohistochemistry. To examine motility of cholangiocarcinoma cells, we employed Boyden chamber, wound healing and Matrigel invasion assays, and a liver xenograft model.

Results

Immunohistochemistry in patient tissues showed WTAP overexpression in cholangiocarcinoma tissues and correlation of WTAP expression with metastasis of cholangiocarcinoma cells. Overexpression or knockdown of WTAP significantly increased or decreased the motility of cholangiocarcinoma cells. Moreover, WTAP overexpression or knockdown significantly increased or decreased tumorigenicity of cholangiocarcinoma cells in an orthotopic xenograft model. Furthermore, microarray study showed that WTAP induce the expressions of MMP7, MMP28, cathepsin H and Muc1.

Conclusion

WTAP is overexpressed in cholangiocarcinoma and regulates motility of cholangiocarcinoma cells

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Acknowledgments

This work was supported by Medical Research Institute Grant (2009-22), Pusan National University Hospital, the medical research centre program of Ministry of Education, Science and Technology/Korea Science and Engineering Foundation (2011-0006190), a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (0920050). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The biospecimens for this study were provided by the Pusan National University Hospital, a member of the National Biobank of Korea, which is supported by the Ministry of Health, Welfare and Family Affairs. All samples derived from the National Biobank of Korea were obtained with informed consent under institutional review board-approved protocols.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Departments of Surgery, School of Medicine, Pusan National University, Busan, Republic of Korea

    Hong-Jae Jo

  2. Departments of Anatomy, School of Medicine, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 626-870, Republic of Korea

    Hye-Eun Shim, Myoung-Eun Han, Hyun-Jung Kim, Ki-Sun Kim, Sungmin Baek & Sae-Ock Oh

  3. Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 626-870, Republic of Korea

    Hye-Eun Shim, Myoung-Eun Han, Hyun-Jung Kim, Sungmin Baek & Sae-Ock Oh

  4. Departments of Pathology, School of Medicine, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 626-870, Republic of Korea

    Kyung-Un Choi

  5. Departments of Forensic Medicine, School of Medicine, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 626-870, Republic of Korea

    Gi-Yeong Hur

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  1. Hong-Jae Jo
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Corresponding author

Correspondence to Sae-Ock Oh.

Additional information

H.-J. Jo and H.-E. Shim equally contributed to this work.

Electronic supplementary material

535_2013_748_MOESM1_ESM.pdf

Supplementary Fig. 1. Staining patterns of WTAP in hepatocytes and epithelial cells of the small intestine. Although not all hepatocytes expressed WTAP, its staining pattern in hepatocytes was mostly cytoplasmic or membranous. However the nuclear staining was clearly observed in epithelial cells of the small intestine. Scale bar, 50 μm (PDF 212 kb)

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Jo, HJ., Shim, HE., Han, ME. et al. WTAP regulates migration and invasion of cholangiocarcinoma cells. J Gastroenterol 48, 1271–1282 (2013). https://doi.org/10.1007/s00535-013-0748-7

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  • DOI: https://doi.org/10.1007/s00535-013-0748-7

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