MYC Ran Up the Clock: The Complex Interplay between MYC and the Molecular Circadian Clock in Cancer

International Journal of Molecular Sciences

Jamison B. Burchett¹  Brian J. Altman¹  Amelia M. Knudsen-Clark² 

[1] Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA;Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA;

关键词: MYC;    cancer;    circadian rhythm;    molecular clock;    transcription factor;    chromatin;   

DOI  :  10.3390/ijms22147761

来源: DOAJ

【 摘 要 】

The MYC oncoprotein and its family members N-MYC and L-MYC are known to drive a wide variety of human cancers. Emerging evidence suggests that MYC has a bi-directional relationship with the molecular clock in cancer. The molecular clock is responsible for circadian (~24 h) rhythms in most eukaryotic cells and organisms, as a mechanism to adapt to light/dark cycles. Disruption of human circadian rhythms, such as through shift work, may serve as a risk factor for cancer, but connections with oncogenic drivers such as MYC were previously not well understood. In this review, we examine recent evidence that MYC in cancer cells can disrupt the molecular clock; and conversely, that molecular clock disruption in cancer can deregulate and elevate MYC. Since MYC and the molecular clock control many of the same processes, we then consider competition between MYC and the molecular clock in several select aspects of tumor biology, including chromatin state, global transcriptional profile, metabolic rewiring, and immune infiltrate in the tumor. Finally, we discuss how the molecular clock can be monitored or diagnosed in human tumors, and how MYC inhibition could potentially restore molecular clock function. Further study of the relationship between the molecular clock and MYC in cancer may reveal previously unsuspected vulnerabilities which could lead to new treatment strategies.

【 授权许可】

Unknown