MYC Disrupts the Circadian Clock and Metabolism in Cancer Cells

Ectopic MYC expression disrupts the molecular clock in cancer cells by inducing REV-ERBα, which dampens BMAL1 expression.

• Deregulated MYC or N-MYC expression alters E-box-driven components of the circadian network.
• REV-ERBα is directly induced by MYC, leading to reduced expression and oscillation of BMAL1.
• Knockdown of REV-ERB rescues the disruption of BMAL1 caused by MYC expression.
• High levels of REV-ERBα are associated with poor clinical outcomes in N-MYC-driven neuroblastomas with low BMAL1 expression.
• Reintroducing BMAL1 in neuroblastoma cell lines decreases their ability to form colonies.
• Ectopic MYC also significantly affects glucose metabolism and disrupts glutaminolysis.

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