The interplay of the circadian clock and metabolic tumorigenesis

HighlightsThe circadian clock and cancer cell metabolism mutually regulate each other through regulation of oncogenes or the tumor microenvironment.Dysregulation of the circadian clock broadly impacts cancer cell metabolism and survival.The core clock genes possess noncanonical and transcription activity-independent functions to reprogram cancer cell metabolism.AbstractThe circadian clock and cell metabolism are both dysregulated in cancer cells through intrinsic cell-autonomous mechanisms and external influences from the tumor microenvironment. The intricate interplay between the circadian clock and cancer cell metabolism exerts control over various metabolic processes, including aerobic glycolysis, de novo nucleotide synthesis, glutamine and protein metabolism, lipid metabolism, mitochondrial metabolism, and redox homeostasis in cancer cells. Importantly, oncogenic signaling can confer a moonlighting function on core clock genes, effectively reshaping cellular metabolism to fuel cancer cell proliferation and drive tumor growth. These interwoven regulatory mechanisms constitute a distinctive feature of cancer cell metabolism.