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Oxysterols and Gastrointestinal Cancers Around the Clock
Urša Kovač1, Cene Skubic1, Laura Bohinc1
1Centre for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Frontiers in Endocrinology
|August 6, 2019
Summary
Oxidized sterols and the circadian clock influence gastrointestinal cancers. Understanding their complex interplay offers potential for novel chronotherapies targeting lipid metabolism for personalized cancer treatment.
Area of Science:
- Integrative oncology, focusing on lipid metabolism and circadian rhythms in cancer.
- Gastrointestinal oncology, specifically hepatocellular carcinoma, pancreatic, and colon cancer.
- Molecular endocrinology and chronobiology.
Background:
- Oxidized sterols (oxysterols) play a role in gastrointestinal cancer pathology, but their effects (protective vs. damaging) are context-dependent.
- Circadian clock disruptions are increasingly linked to metabolic dysregulation and cancer development.
- Limited understanding exists regarding the combined influence of oxysterols and the circadian clock on gastrointestinal carcinogenesis.
Purpose of the Study:
- To review the role of oxysterols in hepatocellular carcinoma, pancreatic cancer, and colon cancer.
- To explore how the circadian clock influences carcinogenesis by regulating lipid metabolism.
- To identify potential biomarkers and therapeutic targets at the intersection of oxysterol metabolism and circadian rhythms.
Main Methods:
- Literature review synthesizing research on oxysterols, circadian clock, and gastrointestinal cancers.
- Analysis of the interplay between sterol/oxysterol pathways and circadian regulators like RORs and LXRs.
- Examination of the modulation of oxysterol concentrations and key regulatory proteins (LXR, FXR, OSBP) in cancer patients.
Main Results:
- Oxysterol concentrations and key regulatory proteins (LXR, FXR, OSBP) are altered in gastrointestinal tumors and patient plasma.
- Key molecular links between cholesterol/oxysterol metabolism and the circadian clock involve RORs and LXRs.
- RORs and LXRs are regulated by both sterols/oxysterols and the circadian clock, indicating a complex regulatory network.
Conclusions:
- Oxysterols and the circadian clock are intertwined in gastrointestinal carcinogenesis, presenting new avenues for research.
- Altered oxysterol levels and regulatory proteins suggest potential as biomarkers and drug targets.
- Chronotherapy, considering the timing of drug administration, holds promise for personalized gastrointestinal cancer management.
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