PER2 Circadian Oscillation Sensitizes Esophageal Cancer Cells to Chemotherapy

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...

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Bibliographic Details
Published in:Biology (Basel, Switzerland) Switzerland), 2021-03, Vol.10 (4), p.266
Main Authors: Redondo, Juan Alfonso, Bibes, Romain, Vercauteren Drubbel, Alizée, Dassy, Benjamin, Bisteau, Xavier, Maury, Eleonore, Beck, Benjamin
Format: Article
Language:English
Subjects:
Apoptosis
Cancer therapies
Cell proliferation
Chemotherapy
chronotherapy
circadian clock
Circadian rhythm
Circadian rhythms
Cisplatin
Clock gene
Data analysis
DNA damage
Drinking water
Esophageal cancer
Esophagus
esophagus cancer
Gene expression
Genomes
Medical prognosis
Metabolism
Metastases
Molecular modelling
Oscillations
Penicillin
Period 2 protein
Squamous cell carcinoma
Synchronization
Tumorigenesis
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Summary: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.
ISSN:2079-7737
2079-7737
DOI:10.3390/biology10040266