NIH R01 · 2024
Disruption of the circadian clock in lung cancer
Project Summary Disruption of the molecular circadian clock is indicative of poor prognosis in non-small cell lung cancers (NSCLCs), but direct evidence for a causal link between circadian clock deregulation and malignancy in human cancer is missing. We found that BMAL1 is downregulated in human NSCLCs, indicative of circadian disruption, low BMAL1 is an indicator of aggressive disease and poor prognosis. In addition, deletion of BMAL1 in a mouse model of NSCLC accelerates cancer progression. These data suggest that BMAL1, and by extension, circadian rhythms, exert a tumor-suppressive role in lung cancer. However, how BMAL1 restrains tumorigenesis and the mechanisms involved in suppression…
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