ENSA expression correlates with attenuated tumor propagation in liver cancer

Yao Li Chen, Ming Han Kuo, Ping Yi Lin, Wan Ling Chuang, Chia Chen Hsu, Pei Yi Chu, Chia Huei Lee, Tim H.M. Huang, Yu Wei Leu, Shu Huei Hsiao

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Endosulfine alpha (ENSA) is an endogenous ligand of sulfonylurea receptor that was reported to be associated with an ATP-dependent potassium channel that controls insulin release and the onset of type 2 diabetes. ENSA also interacts with microtubule-associated serine/threonine-protein kinase-like (MASTL) to regulate the cell cycle. Previously, we identified ENSA as a possible bivalent gene in mesenchymal stem cells (MSCs) and hypothesized its methylation might determine cellular differentiation and transformation. Because there was no link between aberrant ENSA expression and tumorigenesis, we aimed to determine if ENSA is abnormally regulated in liver cancer and plays a role in liver cancer propagation. The epigenetic states of the ENSA promoter were evaluated in different cancer cell lines and patient samples. ENSA was overexpressed in a liver cancer cell line, and its interaction with MASTL and possible tumor suppression capabilities were also determined in cultured cells and mice. Distinct ENSA promoter methylation was observed in liver cancer (n = 100 pairs) and breast cancer (n = 100 pairs). ENSA was predominantly hypomethylated in liver cancer but was hypermethylated in breast cancer. Overexpressed ENSA interacts with MASTL and suppresses hepatic tumor growth. We also found that ENSA is hypermethylated in CD90-expressing (CD90+) cells compared to CD90 non-expressing (CD90-) liver cancer cells. These data reveal ENSA methylation changes during hepatic tumor evolution. Overexpressed ENSA suppresses tumor growth in an established hepatic cell line whereas hypermethylated ENSA might help maintain liver cancer initiating cells.

Original languageEnglish (US)
Pages (from-to)56-61
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1-2
StatePublished - Dec 6 2013


  • Chromatin immunoprecipitation
  • DNA methylation
  • Epigenetic
  • Liver cancer

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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