The Circadian Clock Gene, Bmal1, Regulates Intestinal Stem Cell Signaling and Represses Tumor Initiation

Sep 17, 2021Cellular and molecular gastroenterology and hepatology

The Body's Daily Rhythm Gene Bmal1 Controls Intestinal Stem Cell Signals and Helps Prevent Tumors

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Abstract

Loss of Bmal1 or circadian photoperiod increases tumor initiation in colorectal cancer models.

  • The circadian clock gene Bmal1 is associated with the regulation of transcripts involved in intestinal regeneration and stem cell signaling.
  • Tumors lacking Bmal1 exhibit low autonomous clock function and altered signaling pathways.
  • Apc-disrupted tumors show elevated activity of Yes-associated protein 1, indicating changes in Hippo signaling, but reduced Wnt pathway activity.
  • In intestinal organoids, the absence of Bmal1 leads to increased self-renewal dependent on Yes-associated protein 1.

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