Host Circadian Clock as a Control Point in Tumor Progression

Filipski, Elisabeth; King, Vicky; Li, Xiaomei; Granda, Teresa G.; Mormont, Marie‐Christine; Liu, Xuhui; Bruno, Claudio; Hastings, Michael H.; Lévi, Françis

doi:10.1093/jnci/94.9.690

Cited by 379 publications

(283 citation statements)

References 30 publications

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“…It is also associated with an increased incidence of several epithelial cancers (12-15). In mouse models, transplanted tumors grow twice as fast in scn-lesioned mice than in sham-lesioned animals (16). these studies have suggested a close connection between circadian organization and the development of various cancers.…”

Section: Introductionmentioning

confidence: 92%

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Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer

Oshima

2011

Oncol Rep

102

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Abstract. circadian rhythms are daily oscillations in various biological processes, generated by the feedback loops of eight core circadian genes: Period1 (Per1), Period2 (Per2), Period3 (Per3), Cryptochrome1 (Cry1), Cryptochrome2 (Cry2), Clock, Bmal1 and Casein Kinase I ε (CKIε). recent studies have suggested that circadian genes participate in the growth and development of various cancers. this study examined the relations of circadian gene expression to clinicopathological factors and outcomes in patients with colorectal cancer. We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 202 patients with untreated colorectal cancer. the relative expression levels of the circadian genes in the specimens were measured by quantitative real-time, reverse-transcription polymerase chain reaction. expression of the Clock gene and the CKIε gene in cancer tissue were significantly higher compared to that in adjacent normal mucosa. expression of the Per1 and Per3 genes in cancer tissue was significantly lower compared to that in adjacent normal mucosa. Analysis of the relations between clinicopathological features and expression of the eight circadian genes in cancer tissue showed that high expression of the Bmal1 gene and low expression of the Per1 gene correlated with liver metastasis. on analysis of the relations between outcomes and gene expression, high expression of the Per2 gene was associated with significantly better outcomes than low expression of the Per2 gene. overexpression of the Bmal1 gene and reduced expression of the Per1 gene may thus be useful predictors of liver metastasis. Moreover, reduced expression of the Per2 gene may be a predictor of outcomes in patients with colorectal cancer. Introductioncircadian rhythms are daily oscillations in various biologic processes. In mammals, the master circadian pacemaker is located in the suprachiasmatic nuclei (scn) (1). the master circadian clock coordinates peripheral circadian clocks within virtually every cell in the body (2). this coordination is accomplished directly through autonomic nervous system innervation and indirectly through daily rhythmic synthesis and release of an array of hypothalamic, pituitary, and dispersed endocrine hormones (3-6). the molecular mechanism of circadian oscillation in the scn and peripheral cells is based on the feedback loops of eight core circadian genes (3,7,8). these eight genes are Period1 (Per1), Period2 (Per2), Period3 (Per3), Cryptochrome1 (Cry1), Cryptochrome2 (Cry2), Clock, Bmal1, and Casein Kinase I ε (CKIε). the feedback loops of the eight core circadian genes are as follows. the Clock gene remains steady throughout the 24-h day. High levels of Bmal1 promote the formation of Bmal1/clock heterodimers. these heterodimers bind to e-box sequences in the promoters of the Cry and Per genes to activate transcription. Bmal1/clock heterodimers can also inhibit Bmal1 transcription. After transcription and translation, the per proteins accumulate in the cytoplasm and are phosphorylated by...

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Section: Introductionmentioning

confidence: 92%

“…relations between circadian genes and cancer have been demonstrated in recent years. the host circadian clock has been reported to play an important role in the endogenous control of tumor progression (16). As for circadian genes, Bmal1 was shown to be a positive regulator of tumor growth and metastasis in cancer (17).…”

Section: Introductionmentioning

confidence: 99%

Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer

Oshima

2011

Oncol Rep

102

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“…[75][76][77][78][79]), and many of these signals are under circadian clock control [80,81]. An influence of systemic circadian signals is also indicated by experiments in which tumors were transplanted into animals with SCN ablations: the tumors grew faster in the SCN ablated animals than in normal controls [82]. These systemic signals might interact with peripheral clocks or function independently.…”

Section: Central Rhythms and Cell Proliferation: A Role For Hormones?mentioning

confidence: 99%

Glucocorticoids and circadian clock control of cell proliferation: At the interface between three dynamic systems

Dickmeis

Foulkes

2011

Molecular and Cellular Endocrinology

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The circadian clock, an endogenous timekeeper that regulates daily rhythms of physiology, also influences the dynamic release of glucocorticoids. The release of glucocorticoids is characteristically pulsatile and is further modulated in a circadian fashion. A circadian pacemaker in the brain regulates daily rhythms of hypothalamicpituitary-adrenal axis and autonomic nervous system activity that both influence glucocorticoid release from the adrenal gland. This systemic regulation interacts with rhythms in the adrenal gland itself that are driven by its own circadian clock. One function of glucocorticoids is the regulation of cell proliferation. Depending on the tissue, this can involve both negative and positive regulation of a variety of processes, including cell differentiation and cell death. Cell proliferation is also under circadian control, and recent evidence suggests that this regulation may involve glucocorticoid signalling. Here, we review the dynamic processes participating in the interplay between the circadian clock, glucocorticoids and cell proliferation, and we discuss the potential implications for therapy.

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“…Ce syndrome est connu sous le nom de « non-24 hour sleep-wake cycle syndrome » [13]. Selon leur nature et leur degré, une perturbation ou un dysfonctionnement de l'horloge circadienne ont des implications physiologiques : effet de décalages horaires ou du travail posté, troubles de l'humeur, ou risques accrus de cancérogenèse [16,17]. L'effet des rythmes biologiques sur l'action des médicaments est l'objet des recherches en chronopharmacologie [18].…”

Section: Dysfonctionnements De L'horloge Circadienne Chez L'hommeunclassified

Biologie des systèmes et rythmes cellulaires

2010

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Host Circadian Clock as a Control Point in Tumor Progression

Abstract: Disruption of circadian rhythms in mice was associated with accelerated growth of malignant tumors of two types, suggesting that the host circadian clock may play an important role in endogenous control of tumor progression.

Cited by 379 publications

References 30 publications

Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer

Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer

Glucocorticoids and circadian clock control of cell proliferation: At the interface between three dynamic systems

Biologie des systèmes et rythmes cellulaires

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