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In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells
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Extracellular Acidosis Promotes Metastatic Potency via Decrease of the BMAL1 Circadian Clock Gene in Breast Cancer
Yong-Jin Kwon1,2, Eun-Bi Seo1,2, Sun-Ho Kwon1,2
1Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
Cells
|April 23, 2020
Summary
Tumor hypoxia-induced acidosis reduces the circadian gene BMAL1, increasing breast cancer metastasis. Restoring BMAL1 levels by targeting acidic pH or using melatonin may prevent cancer spread.
Area of Science:
- Oncology
- Molecular Biology
- Chronobiology
Background:
- Circadian gene disruption is linked to diseases like cancer.
- Mechanisms of circadian gene reduction in cancer remain unclear.
Purpose of the Study:
- Investigate the impact of tumor hypoxia-induced acidosis on the circadian gene BMAL1.
- Explore strategies to restore BMAL1 levels and inhibit acidosis-mediated breast cancer metastasis.
Main Methods:
- Utilized breast cancer cell lines under hypoxic and acidic conditions.
- Assessed BMAL1 protein levels, stability, and transcription.
- Investigated the role of melatonin and lactate dehydrogenase-A inhibition.
- Evaluated the effect of BMAL1 overexpression on metastasis.
Main Results:
- Hypoxia-induced acidosis decreased BMAL1 levels by reducing protein stability and inhibiting transcription.
- Melatonin prevented BMAL1 reduction by inhibiting lactate dehydrogenase-A.
- BMAL1 overexpression significantly alleviated acidosis-mediated metastasis.
Conclusions:
- Tumor acidosis promotes breast cancer metastasis by reducing BMAL1.
- Targeting tumor acidosis to sustain BMAL1 is a potential strategy for preventing metastasis.
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