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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01121

Dickkopf Homologue 3 (DKK3) acts as a potential tumor suppressor in gallbladder cancer

 Kirti Gondkar1, 2,  Krishna Patel1, 2, Geeta Patil3, Bipin Nair2,  Akhilesh Pandey4, 5, 6, 7,  Harsha Gowda1 and  Prashant Kumar1, 2, 4*
  • 1Institute of Bioinformatics (IOB), India
  • 2Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, India
  • 3Kidwai Memorial Institute of Oncology, India
  • 4Manipal Academy of Higher Education, India
  • 5Department of Laboratory Medicine and Pathology, Mayo Clinic, United States
  • 6Center for Individualized Medicine, Mayo Clinic, United States
  • 7Center for Addiction Medicine, National Institute of Mental Health and Neuro Sciences, India

Gallbladder cancer (GBC) is a common malignancy of biliary tract cancers and its incidence has been rising rapidly worldwide. The prognosis for this disease is dismal as most of the symptoms are non-specific leading to a definitive diagnosis only at a late stage. Loss of DKK3 gene is associated with a possible tumor suppressor role in human cancers. The role and regulation of DKK3 in GBC have not been studied. We found that DKK3 expression levels were low in GBC patients and cell lines. Treatment of GBC cell lines with demethylating agent 5-Aza- 2’-deoxycytidine enhances its expression, establishing the impact of methylation on DKK3 expression. We observed low expression of DKK3 in gallbladder adenocarcinoma tumors and highly invasive GBC cell lines. We showed that overexpression of DKK3 can decrease cell invasion, proliferation and colony-forming ability of GBC cells. Our data thus demonstrated the DKK3 gene is a potential tumor suppressor gene in GBC and aberrant promoter methylation could be involved in its downregulation, which may play a role in the tumorigenesis and aggressiveness of GBC.

Keywords: Gallbladder adenocarcinoma, dickkopf family, biomarker, Methylation, tumorigenesis

Received: 09 Aug 2019; Accepted: 09 Oct 2019.

Copyright: © 2019 Gondkar, Patel, Patil, Nair, Pandey, Gowda and Kumar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Prashant Kumar, Institute of Bioinformatics (IOB), Bangalore, Karnataka, India, prashant@ibioinformatics.org