Tumor suppression by the molecular clock
How does the molecular clock interact with cancer? Does an active clock promote or suppress cancer formation? Many years of studies have shown that shift workers have a higher incidence of cancer, suggesting that a healthy circadian clock may be tumor-suppressive. Recent studies by our lab and other have suggested the same phenomenon in cancer cell lines and in mouse models of cancer. Our research has shown that the common oncogene MYC disrupts the molecular clock (Altman and Hsieh et al, Cell Metabolism, 2015; Altman et al, Nature Communications, 2017).
But what does that mean for tumor cell growth and survival? We will develop models to study the role of the molecular clock in cells driven by MYC, which is known to disrupt the clock, or other oncogenes such as mutant K-RAS, which does not fully disrupt the clock. Through genetic manipulation, we will disrupt the clock where it still exists in cancer cells, and restore it where it has been disrupted (as in MYC-driven cells), to study the role of the clock in tumor cell growth and physiology.
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