International journal of molecular sciences, 2021-03, Vol.22 (6), p.2974
2021
Details
- Autor(en) / Beteiligte
- Titel
- The Circadian Protein PER1 Modulates the Cellular Response to Anticancer Treatments
- Ist Teil von
- International journal of molecular sciences, 2021-03, Vol.22 (6), p.2974
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- The circadian clock driven by the daily light-dark and temperature cycles of the environment regulates fundamental physiological processes and perturbations of these sophisticated mechanisms may result in pathological conditions, including cancer. While experimental evidence is building up to unravel the link between circadian rhythms and tumorigenesis, it is becoming increasingly apparent that the response to antitumor agents is similarly dependent on the circadian clock, given the dependence of each drug on the circadian regulation of cell cycle, DNA repair and apoptosis. However, the molecular mechanisms that link the circadian machinery to the action of anticancer treatments is still poorly understood, thus limiting the application of circadian rhythms-driven pharmacological therapy, or chronotherapy, in the clinical practice. Herein, we demonstrate the circadian protein period 1 (PER1) and the tumor suppressor p53 negatively cross-regulate each other's expression and activity to modulate the sensitivity of cancer cells to anticancer treatments. Specifically, PER1 physically interacts with p53 to reduce its stability and impair its transcriptional activity, while p53 represses the transcription of PER1. Functionally, we could show that PER1 reduced the sensitivity of cancer cells to drug-induced apoptosis, both in vitro and in vivo in NOD scid gamma (NSG) mice xenotransplanted with a lung cancer cell line. Therefore, our results emphasize the importance of understanding the relationship between the circadian clock and tumor regulatory proteins as the basis for the future development of cancer chronotherapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms22062974Titel-ID: cdi_doaj_primary_oai_doaj_org_article_258b7d2949f34c6f8ee5ac84a169db8f
- Format
- –
- Schlagworte
- A549 Cells, Animals, Anticancer properties, Antineoplastic Agents - pharmacology, Antitumor activity, Apoptosis, Apoptosis - drug effects, Biological clocks, Cancer therapies, Carcinogenesis - genetics, Cell cycle, Cell Cycle - drug effects, Cell Line, Tumor, Chemotherapy, chronotherapy, Circadian rhythm, Circadian Rhythm - drug effects, Circadian rhythms, Cisplatin - pharmacology, Deoxyribonucleic acid, DNA, DNA damage, DNA repair, Docetaxel - pharmacology, Drug Chronotherapy, Drugs, Etoposide - pharmacology, Gene expression, Humans, Lung cancer, Mice, Molecular modelling, Neoplasms - genetics, Neoplasms - pathology, Neoplasms - therapy, p53, p53 Protein, period, Period 1 protein, Period Circadian Proteins - genetics, Phosphorylation, Physiology, Protein expression, Proteins, Regulatory proteins, Sensitivity, Transcription, Tumor suppressor genes, Tumor Suppressor Protein p53 - genetics, Tumorigenesis, Xenograft Model Antitumor Assays, Xenografts