J Cancer 2016; 7(2):153-159. doi:10.7150/jca.13748 This issue


DEC1 and DEC2 Crosstalk between Circadian Rhythm and Tumor Progression

Fuyuki Sato1✉, Ujjal K. Bhawal2, Tomohiro Yoshimura1, Yasuteru Muragaki1

1. Department of Pathology, Wakayama Medical University School of Medicine, Wakayama 641-8509, Japan
2. Department of Biochemistry, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
Sato F, Bhawal UK, Yoshimura T, Muragaki Y. DEC1 and DEC2 Crosstalk between Circadian Rhythm and Tumor Progression. J Cancer 2016; 7(2):153-159. doi:10.7150/jca.13748. Available from https://www.jcancer.org/v07p0153.htm

File import instruction


Clock genes, major regulators of circadian rhythm, are involved in tumor progression. We have shown that clock genes basic helix-loop-helix (BHLH) transcription factors, differentiated embryonic chondrocyte gene 1 (DEC1/BHLHE40/Sharp2/Stra13) and DEC2 (BHLHE41/Sharp1) play important roles in circadian rhythm, cell proliferation, apoptosis, hypoxia response, various stresses, and epithelial-to-mesenchymal transition (EMT) of tumor cells. Various stresses, such as exposure to transforming growth factor-beta (TGF-β), hypoxia, cytokines, serum-free, and anti-tumor drugs affect DEC1 and DEC2 expression. An increased or decreased expression of DEC1 and DEC2 regulated tumor progression. However, DEC1 and DEC2 have opposite effects in tumor progression, where the reason behind remains unclear. We found that DEC2 has circadian expression in implanted mouse sarcoma cells, suggesting that DEC2 regulates tumor progression under circadian rhythm. In addition to that, we showed that DEC1 and DEC2 regulate target genes via positive or negative feedback system in tumor progression. We propose that DEC1 and DEC2 act as an accelerator or a brake in tumor progression. In this review, we summarize current progress of knowledge in the function of DEC1 and DEC2 genes in tumor progression.

Keywords: DEC1, DEC2, clock gene, circadian rhythm, immunohistochemistry, tumor progression