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Circadian Misalignment and Metabolic Disorders: A Story of Twisted Clocks
Article

PER2 Circadian Oscillation Sensitizes Esophageal Cancer Cells to Chemotherapy

1
Institute of Interdisciplinary Research (IRIBHM), Faculty of Medicine, Erasme Campus of Université Libre de Bruxelles (ULB), 808 Route de Lennik, 1070 Brussels, Belgium
2
Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research (IREC), Faculty of Medicine, Bruxelles-Woluwe Campus of Université catholique de Louvain (UCLouvain), 55 Avenue Hippocrate, 1200 Woluwe-Saint-Lambert, Belgium
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Gianluigi Ubaldo Mazzoccoli
Biology 2021, 10(4), 266; https://doi.org/10.3390/biology10040266
Received: 1 February 2021 / Revised: 11 March 2021 / Accepted: 24 March 2021 / Published: 26 March 2021
(This article belongs to the Special Issue Circadian Disruption and Metabolic Disorders)
There are growing evidences that the circadian rhythm modulates key cellular processes in physiological and pathological conditions. Here, we characterized the consequences of the daily oscillations of the clock-related gene PER2 in esophageal cancer cells and found that chemotherapy is more efficient when PER2 expression is low. These results suggest that chronotherapy might be used to potentiate the impact of current chemotherapy regimen.
Esophageal squamous cell carcinoma (eSCC) accounts for more than 85% cases of esophageal cancer worldwide and the 5-year survival rate associated with metastatic eSCC is poor. This low survival rate is the consequence of a complex mechanism of resistance to therapy and tumor relapse. To effectively reduce the mortality rate of this disease, we need to better understand the molecular mechanisms underlying the development of resistance to therapy and translate that knowledge into novel approaches for cancer treatment. The circadian clock orchestrates several physiological processes through the establishment and synchronization of circadian rhythms. Since cancer cells need to fuel rapid proliferation and increased metabolic demands, the escape from circadian rhythm is relevant in tumorigenesis. Although clock related genes may be globally repressed in human eSCC samples, PER2 expression still oscillates in some human eSCC cell lines. However, the consequences of this circadian rhythm are still unclear. In the present study, we confirm that PER2 oscillations still occur in human cancer cells in vitro in spite of a deregulated circadian clock gene expression. Profiling of eSCC cells by RNAseq reveals that when PER2 expression is low, several transcripts related to apoptosis are upregulated. Consistently, treating eSCC cells with cisplatin when PER2 expression is low enhances DNA damage and leads to a higher apoptosis rate. Interestingly, this process is conserved in a mouse model of chemically-induced eSCC ex vivo. These results therefore suggest that response to therapy might be enhanced in esophageal cancers using chronotherapy. View Full-Text
Keywords: circadian clock; esophagus cancer; squamous cell carcinoma; apoptosis; chemotherapy; chronotherapy circadian clock; esophagus cancer; squamous cell carcinoma; apoptosis; chemotherapy; chronotherapy
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MDPI and ACS Style

Redondo, J.A.; Bibes, R.; Vercauteren Drubbel, A.; Dassy, B.; Bisteau, X.; Maury, E.; Beck, B. PER2 Circadian Oscillation Sensitizes Esophageal Cancer Cells to Chemotherapy. Biology 2021, 10, 266. https://doi.org/10.3390/biology10040266

AMA Style

Redondo JA, Bibes R, Vercauteren Drubbel A, Dassy B, Bisteau X, Maury E, Beck B. PER2 Circadian Oscillation Sensitizes Esophageal Cancer Cells to Chemotherapy. Biology. 2021; 10(4):266. https://doi.org/10.3390/biology10040266

Chicago/Turabian Style

Redondo, Juan A., Romain Bibes, Alizée Vercauteren Drubbel, Benjamin Dassy, Xavier Bisteau, Eleonore Maury, and Benjamin Beck. 2021. "PER2 Circadian Oscillation Sensitizes Esophageal Cancer Cells to Chemotherapy" Biology 10, no. 4: 266. https://doi.org/10.3390/biology10040266

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