PER2 Circadian Oscillation Sensitizes Esophageal Cancer Cells to Chemotherapy
| Autor: | Alizée Vercauteren Drubbel, Juan Alfonso Redondo, Benjamin Dassy, Xavier Bisteau, Eleonore Maury, Benjamin Beck, Romain Bibes |
|---|---|
| Přispěvatelé: | UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition |
| Rok vydání: | 2021 |
| Předmět: |
squamous cell carcinoma
Circadian clock Circadian clocl Apoptosis Sciences biomédicales en général Biology chemotherapy medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Squamous cell carcinoma circadian clock medicine Chemotherapy Circadian rhythm lcsh:QH301-705.5 Survival rate 030304 developmental biology Chronotherapy Cisplatin 0303 health sciences chronotherapy General Immunology and Microbiology apoptosis Esophageal cancer medicine.disease Esophagus cancer 3. Good health PER2 esophagus cancer lcsh:Biology (General) 030220 oncology & carcinogenesis Cancer cell Cancer research General Agricultural and Biological Sciences Carcinogenesis medicine.drug |
| Zdroj: | Biology, Vol 10, Iss 266, p 266 (2021) Biology Biology, 10 (4 Volume 10 Issue 4 Biology, Vol. 10, no.4, p. 266 [1-18] (2021) |
| ISSN: | 2079-7737 |
| DOI: | 10.3390/biology10040266 |
| Popis: | 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. info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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