Clinicopathological significance of circadian rhythm‐related gene expression levels in patients with epithelial ovarian cancer

Tokunaga, Hideki; Takebayashi, Yuji; Utsunomiya, Hiroki; Akahira, Jun Ichi; Higashimoto, Masashi; Mashiko, Miyuki; Itō, Kiyoshi; Niikura, Hitoshi; Takenoshita, S; Yaegashi, Nobuo

doi:10.1080/00016340802348286

Cited by 75 publications

(56 citation statements)

References 46 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, recent studies identify BMAL1 as a putative tumor suppressor (Savvidis and Koutsilieris, 2012; Yeh et al, 2014). Ovarian cancers have altered circadian gene expression and oscillation compared to normal tissue, but the functional significance and mechanism for these alterations were not established (Tokunaga et al, 2008). Still other studies found circadian gene expression alterations in cancers such as pancreatic, prostate, and glioma (Savvidis and Koutsilieris, 2012).…”

Section: Introductionmentioning

confidence: 99%

MYC Disrupts the Circadian Clock and Metabolism in Cancer Cells

et al. 2015

View full text Add to dashboard Cite

Summary The MYC oncogene encodes MYC, a transcription factor that binds the genome through sites termed E-boxes (5′-CACGTG-3′), which are identical to the binding sites of the heterodimeric CLOCK-BMAL1 master circadian transcription factor. Hence, we hypothesized that ectopic MYC expression perturbs the clock by deregulating E-box-driven components of the circadian network in cancer cells. We report here that deregulated expression of MYC or N-MYC disrupts the molecular clock in vitro by directly inducing REV-ERBα to dampen expression and oscillation of BMAL1, and this could be rescued by knockdown of REV-ERB. REV-ERBα expression predicts poor clinical outcome for N-MYC-driven human neuroblastomas that have diminished BMAL1 expression, and reexpression of ectopic BMAL1 in neuroblastoma cell lines suppresses their clonogenicity. Further, ectopic MYC profoundly alters oscillation of glucose metabolism and perturbs glutaminolysis. Our results demonstrate an unsuspected link between oncogenic transformation and circadian and metabolic dysrhythmia, which we surmise to be advantageous for cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

MYC Disrupts the Circadian Clock and Metabolism in Cancer Cells

et al. 2015

View full text Add to dashboard Cite

show abstract

“…39 Alterations in clock genes in tumors versus healthy tissue can cause increased susceptibility to develop cancer and poor patient survival. This was shown for colorectal cancer, 40,41 chronic lymphocytic leukemia, 42 epithelial ovarian cancer, 43 and breast cancer. 44 In various epidemiological studies, it was shown that single nucleotide polymorphisms in clock genes are associated with higher cancer risk for prostate cancer (CRY2 rs1401417: G.C, 1.7-fold higher risk), 45 breast cancer (NPAS2 Ala394Thr), 46 non-Hodgkin's lymphoma (CRY2 rs11038689, rs7123390, rs1401417), 47 and colorectal carcinoma (CLOCK1 311T.C, CC 2.78-fold and TC 1.78-fold higher risk).…”

Section: Circadian Rhythms and Cancermentioning

confidence: 71%

Circadian rhythms and new options for novel anticancer therapies

Zmrzljak¹

2015

CPT

View full text Add to dashboard Cite

The patterns of activity/sleep, eating/fasting, etc show that our lives are under the control of an internal clock. Cancer is a systemic disease that affects sleep, feeding, and metabolism. All these processes are regulated by the circadian clock on the one hand, but on the other hand, they can serve as signals to tighten up the patient's circadian clock by robust daily routine. Usually, anticancer treatments take place in hospitals, where the patient's daily rest/activity pattern is changed. However, it has been shown that oncology patients with a disturbed circadian clock have poorer survival outcomes. The administration of different anticancer therapies can disturb the circadian cycle, but many cases show that circadian rhythms in tumors are deregulated per se. This fact can be used to plan anticancer therapies in such a manner that they will be most effective in antitumor action, but least toxic for the surrounding healthy tissue. Metabolic processes are highly regulated to prevent waste of energy and to ensure sufficient detoxification; as a consequence, xenobiotic metabolism is under tight circadian control. This gives the rationale for planning the administration of anticancer therapies in a chronomodulated manner. We review some of the potentially useful clinical praxes of anticancer therapies and discuss different possible approaches to be used in drug development and design in the future.

show abstract

“…Clock genes regulate cell proliferation and apoptosis by controlling a number of cell cyclerelated genes, cell cycle checkpoints, and tumor-suppressor genes that mediate response to DNA damage. Chronic exposure to shift work may disrupt circadian rhythms and stimulate tumor development and progression, partly mediated by epigenetic changes [2,3,[5][6][7][8][9][10].…”

Section: Clock Genesmentioning

confidence: 99%

Sleep Disorders and Cancer

Martínez‐García

Campos‐Rodríguez

Almendros

2016

Curr Sleep Medicine Rep

View full text Add to dashboard Cite

There is a growing evidence that sleep disorders are associated with an increased incidence and accelerated cancer progression. In the light of the previously established relationship between hypoxemia and cancer, obstructive sleep apnea and its main consequence, intermittent hypoxia, could be associated with a poorer prognosis or higher incidence of cancer. From this pathophysiological starting point, and in the light of animal studies that confirmed this association, two separate research groups observed in large-scale clinical and epidemiological series that the degree of nighttime hypoxia found in patients with obstructive sleep apnea was associated with a higher incidence of cancer, as well as a higher mortality rate although their retrospective nature means that they should be considered with caution. A study currently in progress with a large group of patients with melanoma may soon cast new light on the existence or not of this association and its underlying pathophysiological mechanisms.

show abstract

Clinicopathological significance of circadian rhythm‐related gene expression levels in patients with epithelial ovarian cancer

Abstract: The antiphase expression of cry1 and Bmal1 may be preserved in ovarian cancers. The combination of cry1 and Bmal1 expression might become a possible prognostic marker in epithelial ovarian cancer.

Cited by 75 publications

References 46 publications

MYC Disrupts the Circadian Clock and Metabolism in Cancer Cells

MYC Disrupts the Circadian Clock and Metabolism in Cancer Cells

Circadian rhythms and new options for novel anticancer therapies

Sleep Disorders and Cancer

Contact Info

Product

Resources

About