Abstract 456: Functional analysis of DEC1 and DEC2 in cancer metabolism

Abstract

Abstract Basic helix-loop-helix (bHLH) transcription factor DEC1 (bHLHE40/Stra13/Sharp2) and DEC2 (bHLHE41/Sharp1) are clock genes that show a circadian rhythm in various tissues. However, the function of DEC1 and DEC2 in metabolism has not been poorly understood. AMP-activated protein kinase (AMPK) activity plays important roles in the metabolic process and circadian rhythm. However, how circadian rhythm of phosphorylation of AMPK (pAMPK) is regulated has been yet understood. The aim of this study is to investigate whether there is a direct correlation between DEC1 and DEC2 expression and AMPK activity in normal and cancer cells. There was an inverse relationship between DEC1 expression and AMPK activity. DEC1 protein and pAMPK showed a circadian rhythm in the mouse liver with different peak levels. Knocking down DEC1 expression increased pAMPK, whereas overexpression of DEC1 decreased it. DEC1 bound to the E-box of the LKB1 promoter, decreased LKB1 activity and total protein levels. In addition, pAMPK immunoreactivity was strongly detected in the liver and lung of DEC2 knockout mice compared with that of wild-type mice. Interestingly, medium change induced the circadian rhythm of DEC2, but not DEC1 in cancer cells. We conclude that DEC1 and DEC2 negatively regulates AMPK activity via LKB1, and play important roles in cancer cell metabolism. Citation Format: Fuyuki Sato, Yasueru Muragaki. Functional analysis of DEC1 and DEC2 in cancer metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 456. doi:10.1158/1538-7445.AM2017-456