Epigenetic regulation of the novel tumor suppressor cysteine dioxygenase 1 in esophageal squamous cell carcinoma

Tumour Biol. 2015 Sep;36(10):7449-56. doi: 10.1007/s13277-015-3443-x. Epub 2015 Apr 24.

Abstract

Esophageal squamous cell carcinoma (ESCC), the most common subtype of esophageal cancer in East Asian countries, is still associated with a poor prognosis because of the high frequency of lymph node metastasis and invasion. In our previous study, we identified a novel methylation gene, cysteine dioxygenase 1 (CDO1) that is involved in the conversion of cysteine to cysteine sulfinate, and plays a key role in taurine biosynthesis. Decreased expression of CDO1 was observed in ESCC cell lines and tumors derived from patient tissues, and CDO1 silencing could be reversed by treatment with 5-aza-2'-deoxycytidine in six ESCC cell lines. Forced expression of CDO1 in three different ESCC cell lines, TE-4, TE-6, and TE-14, significantly decreased tumor cell growth, cell migration, invasion, and the ability of colony formation. Although CDO1 expression was not found to significantly correlate with survival in ESCC patients, our results suggest that methylation-regulated CDO1 may represent a functional tumor suppressor and a potentially valuable diagnostic biomarker for ESCC.

Keywords: Biomarker; Cysteine dioxygenase 1; Esophageal squamous cell carcinoma; Hypermethylation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • Cell Movement
  • Cell Proliferation
  • Cysteine Dioxygenase / genetics*
  • DNA Methylation*
  • Epigenesis, Genetic / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • RNA, Messenger
  • CDO1 protein, human
  • Cysteine Dioxygenase