Sunday, July 04, 2021

Scientists reveal how internal biological clock may suppress tumor growth

Good news! Cancer is history!

"Those who engage in long-term, rotational shift work, such as nursing or firefighting, are at increased risk of developing cancer, but the biological roots of this phenomenon have remained largely unknown.
Now, new research ... demonstrates a clear link between the circadian clock and the body’s tumor suppression system, with the potential to accelerate cancer cell growth. ...
the new research shows how mutant forms of the circadian clock gene CRY2 found in human tumors are able to dampen the activity of a key tumor suppressor gene, P53. ...
“This is the first study to investigate point mutations in a core clock gene that have been reported in human cancers,” ... “The impact of these genetic changes on P53 activity is truly remarkable and indicates a striking regulation of tumor suppression by the circadian clock.” ..."

"... The circadian repressors CRY1 and CRY2 evolved from light-activated DNA-repair enzymes, suggesting that they may be involved. Here, we demonstrate that missense mutations in CRY2 reported in The Cancer Genome Atlas suppress P53 target-gene expression and enhance the growth of MYC-transformed fibroblasts. Our identification of point mutations in CRY2 in human tumors that influence P53 activity and cell growth provides evidence for a clinically relevant molecular connection between CRYs and P53. ...
Disruption of circadian rhythms increases the risk of several types of cancer. Mammalian cryptochromes (CRY1 and CRY2) are circadian transcriptional repressors that are related to DNA-repair enzymes. While CRYs lack DNA-repair activity, they modulate the transcriptional response to DNA damage, and CRY2 can promote SKP1 cullin 1–F-box (SCF)FBXL3-mediated ubiquitination of c-MYC and other targets. Here, we characterize five mutations in CRY2 observed in human cancers in The Cancer Genome Atlas. We demonstrate that two orthologous mutations of mouse CRY2 (D325H and S510L) accelerate the growth of primary mouse fibroblasts expressing high levels of c-MYC."

Scientists reveal how internal biological clock may suppress tumor growth | Scripps Research New discovery helps explain how disruption to daily biological rhythms could lead to increased risk of cancer.

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