Entrainment of breast (cancer) epithelial cells detects distinct circadian oscillation patterns for clock and hormone receptor genes

Rossetti, Stefano; Esposito, Joseph J.; Corlazzoli, Francesca; Gregorski, Alex; Sacchi, Nicoletta

doi:10.4161/cc.11.2.18792

Cited by 50 publications

(72 citation statements)

References 48 publications

(59 reference statements)

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“…At this point it is not clear whether the idea of functional clocks in tumors applies to other tumor types. Recent studies of mammary epithelial cells have demonstrated robust oscillation in normal cells and the loss of rhythmic gene expression in cancer cell lines (Rossetti et al, 2012). It is important to note that these studies are limited to cell culture and the ability of breast tumor cells to be entrained in the context of an organism has not been tested.…”

Section: Discussionmentioning

confidence: 99%

Daily rhythms are retained both in spontaneously developed sarcomas and in xenografts grown in immunocompromised SCID mice

Comas

Kuropatwinski

Wrobel

et al. 2014

Chronobiology International

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The circadian clock generates and regulates many daily physiological, metabolic and behavioral rhythms as well as acute responses to various types of stresses including those induced by anticancer treatment. It has been proposed that modulatory function of the clock may be used for improving the therapeutic efficacy of established anti-cancer treatments. In order to rationally exploit this mechanism, more information is needed to fully characterize the functional status of the molecular clock in tumors of different cellular origin; however, the data describing tumor clocks are still inconsistent. Here we tested the status of clock in two models of tumors derived from connective tissue: sarcomas spontaneously developed in p53-deficient mice and human fibrosarcoma cells grown as xenografts in immunocompromised severe combined immunodeficient (SCID) mice. We show that both types of tumors retain a functional clock, which is synchronized in phase with normal tissues. We also show that spontaneously developed tumors are not only oscillating in the context of an organism where they receive hormonal and metabolic signals but continue oscillating ex vivo in tissue explants demonstrating that tumors have functional clocks capable of timing all their functions. We also provide evidence that similar to liver, tumors can be synchronized by food availability independent of the central pacemaker in the suprachiasmatic nuclei (SCN). These data provide the basis for the design of anticancer therapies that take into account the circadian metabolic and physiological patterns of both the tumor and normal tissues.

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Section: Discussionmentioning

confidence: 99%

Daily rhythms are retained both in spontaneously developed sarcomas and in xenografts grown in immunocompromised SCID mice

Comas

Kuropatwinski

Wrobel

et al. 2014

Chronobiology International

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“…Since there is extensive experimental evidence that gene deregulation influenced by the circadian clock is involved in the development of cancer [18][19][20], the molecular mechanism of the circadian rhythm disruption and its propagation due to cell-to-cell signaling should become an essential factor in the transformation of cells. In mammals, it is now known that if the connection between the peripheral clocks and the pacemaker in SCN is destroyed, the organism has a high risk of cancer.…”

Section: General Principlesmentioning

confidence: 99%

“…Here, the reactions of dimerization and dedimerization are given by (19) and (20); the dynamics of operator-sites during binding/unbinding of dimers are described by (21) and (22); the time-delayed synthesis of proteins is given by (23); the linear and non-linear degradations are described by (24) and (25), respectively. Assuming that reactions of dimerization and binding/unbinding are fast compared to the processes of production and degradation of proteins, so that they quickly reach a local equilibrium, we obtain two delay differential equations (in fact, the procedure of derivation is similar to those for Circadian model I):…”

Section: Circadian Model Ii: Two-gene Oscillator With Positive and Nementioning

confidence: 99%

“…It has been recognized in recent years that core circadian genes are important in tissue homeostasis and tumorigenesis. In recent years, a significant number of works have shown that disruption of the circadian mechanism is implicated in gene deregulation, leading to the development of cancer and other diseases [18][19][20]. The main idea of this work is that tumor occurrence is induced by a local disruption of the circadian rhythm in the epithelial tissue when the control of the peripheral circadian oscillators by the suprachiasmatic nuclei weakens or vanishes completely.…”

Section: Introductionmentioning

confidence: 99%

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Multiscale modeling of tumor growth induced by circadian rhythm disruption in epithelial tissue

et al. 2015

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We propose a multiscale chemo-mechanical model of cancer tumor development in epithelial tissue. The model is based on the transformation of normal cells into a cancerous state triggered by a local failure of spatial synchronization of the circadian rhythm. The model includes mechanical interactions and a chemical signal exchange between neighboring cells, as well as a division of cells and intercalation that allows for modification of the respective parameters following transformation into the cancerous state. The numerical simulations reproduce different dephasing patterns-spiral waves and quasistationary clustering, with the latter being conducive to cancer formation. Modification of mechanical properties reproduces a distinct behavior of invasive and localized carcinoma.

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“…Consequently, both tumors exhibit a disrupted inner clock. According to Rossetti et al, drugs in hormone therapies targeting ER-alpha-positive breast cancer may be less effi cient because the tumor cells have insuffi cient estrogen signaling due to impaired accumulation of ER-alpha in a circadian manner (Rossetti et al 2012b ).…”

Section: Night Shift and Breast Cancermentioning

confidence: 99%

Night Shifts and Melatonin: Relevance to Age and Breast Cancer

Engin

2015

Tryptophan Metabolism: Implications for Biological Processes, Health and Disease

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In mammals, melatonin is synthesized not only in the pineal gland but also in many other parts of the body. The nocturnal synthesis and release of melatonin by the pineal gland are tightly controlled by the central suprachiasmatic nucleus (SCN) clock. This circadian pacemaker encodes rhythmic output in accordance with light input. Environmental light is sensed by an intrinsically photosensitive retinal ganglion cells (ipRGCs). Circadian rhythmicity in the SCN originates from the interaction of a defi ned set of "clock genes." Melatonin is able to alter the levels of various circadian rhythm genes by re-synchronizing a rhythmic pattern of clock gene expression. Silent mating type information regulation 2 homolog-1 (Sirt1), a nicotinamide adenine dinucleotide [NAD + ]-dependent histone deacetylase, is required for circadian clock gene expression. Altered circadian rhythm regulation plays a critical role in carcinogenesis. Melatonin signifi cantly inhibits Sirt1 protein transcription and activity in multiple human cancer cell lines. However, light is able to either suppress or synchronize melatonin production according to the light schedule. Therefore in industrialized countries, night-shift workers are at high risk for circadian disruption. Epidemiological studies displayed that the increase in breast cancer risk in night-shift workers is associated with exposure to light at night. Furthermore age-related changes refl ect a decline in pacemaker amplitude, due to alteration of SCN functions and systems under its control. Consequently dysfunction of endogenous clocks, melatonin receptor polymorphisms, and age-associated decline of melatonin synthesis are already increased risks of breast cancer.

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Entrainment of breast (cancer) epithelial cells detects distinct circadian oscillation patterns for clock and hormone receptor genes

Cited by 50 publications

References 48 publications

Daily rhythms are retained both in spontaneously developed sarcomas and in xenografts grown in immunocompromised SCID mice

Daily rhythms are retained both in spontaneously developed sarcomas and in xenografts grown in immunocompromised SCID mice

Multiscale modeling of tumor growth induced by circadian rhythm disruption in epithelial tissue

Night Shifts and Melatonin: Relevance to Age and Breast Cancer

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