The DACH/EYA/SIX gene network and its role in tumor initiation and progression

Int J Cancer. 2016 Mar 1;138(5):1067-75. doi: 10.1002/ijc.29560. Epub 2015 Jun 12.

Abstract

The functional abnormality of developmental genes is a common phenomenon in cancer initiation and progression. The retinal determination gene network (RDGN) is a key signal in Drosophila eye specification, and this conservative pathway is also required for the development of multiple organs in mammalian species. Recent studies demonstrated that aberrant expressions of RDGN components in vertebrates, mainly Dach, Six, and Eya, represent a novel tumor signal. RDGN regulates proliferation, apoptosis, tumor growth and metastasis through interactions with multiple signaling pathways in a co-ordinated fashion; Dach acts as a tumor suppressor, whereas Six and Eya function as oncogenes. Clinical analyses demonstrated that the expression levels of RDGN correlate with tumor stage, metastasis and survival, suggesting that combinational detection of this pathway might be used as a promising biomarker for the stratification of therapy and for the prediction of the prognosis of cancer patients.

Keywords: DACH1; EMT; EYA1; SIX1; cancer stem cell.

Publication types

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

MeSH terms

  • Animals
  • Cell Movement
  • Epithelial-Mesenchymal Transition
  • Eye Proteins / genetics*
  • Eye Proteins / physiology
  • Gene Regulatory Networks*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / physiology
  • Neoplasm Invasiveness
  • Neoplasms / etiology*
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / physiology
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases / physiology
  • Signal Transduction
  • Transcription Factors / genetics*
  • Transcription Factors / physiology

Substances

  • DACH1 protein, human
  • Eye Proteins
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • SIX1 protein, human
  • Transcription Factors
  • EYA1 protein, human
  • Protein Tyrosine Phosphatases