Evaluating Circadian Oscillators in Cancer Stem Cells - Evaluating Circadian Oscillators in Cancer Stem Cells - Open Access Pub

Cancer is influenced by the ability of cells to maintain circadian rhythms in molecular and metabolic processes. Disturbance of the underlying circadian timing mechanism in circadian clock cells leads to a higher frequency and more rapid progression of cancer. Cancer stem cells with properties of embryonic and somatic stem cells have been implicated as tumor initiators in several types of cancers. Although tumors are reported to have disorganized circadian rhythms, evidence of in vitro circadian rhythms in cancer stem cells of gliomas was recently presented. The possibility and consequences of circadian clocks functioning in cancer stem cells within tumors is examined, and the possible benefits to these cells from circadian timing is discussed in relation to cancer treatments. DOI10.14302/issn.2574-4372.jesr-14-607 Circadian Rhythms and Cancer Cell Survival The relationship between circadian rhythms and cancer is generally thought to be one of mutual exclusion. Circadian rhythms are approximately 24-hour oscillations in physiology or behavior that are reported to be either poorly defined or lacking in cancer cells 1, 2, 3. Similarly, robust circadian rhythms are thought to suppress carcinogenesis and tumor growth 4, 5, 6. The benefits provided by circadian timing have been discussed and reviewed elsewhere in relation to events external to the organism 7, 8, 9, 10. The ability to anticipate daily occurrence of food sources, favorable temperatures, and mates or avoid predictable hazards such as predators and environmental stressors are just some of the potential benefits offered by the clock that provide adaptive value. Probably because of adversely timed light exposure and the disrupted circadian timing system that follows 11, individuals working night shifts are reported to have higher incidences of breast cancer 12, 13 and non-Hodgkin’s lymphoma 14. A major cause appears to be light-induced alterations in the daily oscillations of the hormone melatonin 15, 19, a possible cancer suppressor 20, 21, 22, although not all studies support this mechanism 23. Altered rhythms in cortisol and other factors that provide timing information throughout the body may also be involved in the effects of light exposure and circadian disturbances during nighttime work 24, 25, 26. Circadian timing disruption might indirectly promote cancer by fostering obesity and the metabolic syndrome 27 or by shortening sleep duration 28, 29, 30. A more proximal cause is shown by the loss of circadian timing in mice or cancer cell lines, through knockout of critical core genes within