Global DNA hypomethylation coupled to cellular transformation and metastatic ability

FEBS Lett. 2015 Dec 21;589(24 Pt B):4053-60. doi: 10.1016/j.febslet.2015.11.020. Epub 2015 Nov 19.

Abstract

Global DNA hypomethylation and DNA hypermethylation of promoter regions are frequently detected in human cancers. Although many studies have suggested a contribution to carcinogenesis, it is still unclear whether the aberrant DNA hypomethylation observed in tumors is a consequence or a cause of cancer. Here, we show that the enforced expression of Stella (also known as PGC7 and Dppa3) induced not only global DNA demethylation but also transformation of NIH3T3 cells. Furthermore, overexpression of Stella enhanced the metastatic ability of B16 melanoma cells, presumably through the induction of metastasis-related genes. These results provide new insights into the function of global DNA hypomethylation in carcinogenesis.

Keywords: DNA hypomethylation; Metastasis; Stella; Transformation.

Publication types

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

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Chromosomal Proteins, Non-Histone
  • Clone Cells
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation*
  • Down-Regulation*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neoplasm Metastasis* / pathology
  • Neoplasm Transplantation
  • Promoter Regions, Genetic*
  • Proteins / antagonists & inhibitors
  • Proteins / genetics
  • Proteins / metabolism*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • RNA Interference
  • RNA, Small Interfering
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Tumor Burden

Substances

  • Chromosomal Proteins, Non-Histone
  • DPPA3 protein, human
  • Proteins
  • RNA, Small Interfering
  • Recombinant Proteins
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • Proto-Oncogene Proteins p21(ras)