Fig. 3

Circadian rhythms and cancer. This figure shows some examples on how circadian rhythm alterations contribute to the appearance of cancer hallmarks. a Circadian rhythms and cell cycle: DNA replication and cell cycle present a specific circadian pattern. Indeed, the expression of regulators of DNA replication and cell cycle shows circadian rhythms [67,68,69,70]. Moreover, circadian cycle genes play an important role in the regulation of some cell cycle genes [71, 72]. b Circadian rhythms and DNA repair: DNA repair, DNA damage response, and the circadian cycle are tightly connected. As observed for cell cycle regulators, the expression (mRNA and protein) of DNA repair genes shows circadian patterns [69]. Reciprocally, DNA damage can affect the circadian clock [73, 74]. c Circadian rhythm and metabolism: The circadian rhythm influences a wide range of metabolic processes, such as the mitochondrial, glucose, amino acid, and lipid metabolisms as well as the Krebs cycle [75, 76]. As the metabolic needs of cancer cells are different from those of normal cells, the impact of circadian disruption should be taken into account when studying their metabolism in the tumor environment. The hypoxic tumor microenvironment and the activation of hypoxia-inducible factors (HIFs) play a regulatory role in tumor-linked metabolism and angiogenesis [65, 77]. d Circadian rhythm and apoptosis: alterations of circadian clock components influence the expression of apoptosis-related genes