Circadian disruption: from mouse models to molecular mechanisms and cancer therapeutic targets

Cancer Metastasis Rev. 2023 Mar;42(1):297-322. doi: 10.1007/s10555-022-10072-0. Epub 2022 Dec 14.

Abstract

The circadian clock is a timekeeping system for numerous biological rhythms that contribute to the regulation of numerous homeostatic processes in humans. Disruption of circadian rhythms influences physiology and behavior and is associated with adverse health outcomes, especially cancer. However, the underlying molecular mechanisms of circadian disruption-associated cancer initiation and development remain unclear. It is essential to construct good circadian disruption models to uncover and validate the detailed molecular clock framework of circadian disruption in cancer development and progression. Mouse models are the most widely used in circadian studies due to their relatively small size, fast reproduction cycle, easy genome manipulation, and economic practicality. Here, we reviewed the current mouse models of circadian disruption, including suprachiasmatic nuclei destruction, genetic engineering, light disruption, sleep deprivation, and other lifestyle factors in our understanding of the crosstalk between circadian rhythms and oncogenic signaling, as well as the molecular mechanisms of circadian disruption that promotes cancer growth. We focused on the discoveries made with the nocturnal mouse, diurnal human being, and cell culture and provided several circadian rhythm-based cancer therapeutic strategies.

Keywords: BMAL1; CLOCK; Cancer target; Circadian rhythm; Mouse models.

Publication types

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

MeSH terms

  • Animals
  • Circadian Rhythm* / genetics
  • Disease Models, Animal
  • Humans
  • Mice
  • Neoplasms* / genetics
  • Neoplasms* / therapy
  • Suprachiasmatic Nucleus / physiology