Hey Factors at the Crossroad of Tumorigenesis and Clinical Therapeutic Modulation of Hey for Anticancer Treatment

Mol Cancer Ther. 2017 May;16(5):775-786. doi: 10.1158/1535-7163.MCT-16-0576.


Hairy and Enhancer-of-split related with YRPW motif (Hey) transcription factors are important regulators of stem cell embryogenesis. Clinical relevance shows that they are also highly expressed in malignant carcinoma. Recent studies have highlighted functions for the Hey factors in tumor metastasis, the maintenance of cancer cell self-renewal, as well as proliferation and the promotion of tumor angiogenesis. Pathways that regulate Hey gene expression, such as Notch and TGFβ signaling, are frequently aberrant in numerous cancers. In addition, Hey factors control downstream targets via recruitment of histone deacetylases (HDAC). Targeting these signaling pathways or HDACs may reverse tumor progression and provide clinical benefit for cancer patients. Thus, some small molecular inhibitors or monoclonal antibodies of each of these signaling pathways have been studied in clinical trials. This review focuses on the involvement of Hey proteins in malignant carcinoma progression and provides valuable therapeutic information for anticancer treatment. Mol Cancer Ther; 16(5); 775-86. ©2017 AACR.

Publication types

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

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Carcinogenesis / genetics*
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Cycle Proteins / genetics*
  • Cell Proliferation / genetics
  • Histone Deacetylases / genetics
  • Humans
  • Neoplasm Metastasis
  • Receptors, Notch / genetics
  • Signal Transduction / genetics
  • Transforming Growth Factor beta / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • HEY1 protein, human
  • Receptors, Notch
  • Transforming Growth Factor beta
  • Histone Deacetylases