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Cancer checkpoint
Date:4/5/2013

cle of division and growth.

Blocking the cell cycle at this juncture is important. If cell growth after DNA damage goes unchecked, proliferation of impaired cells can lead to cancer. When SIRT4 works properly, this chain of events is broken before bad cells and their abnormal genes multiply. SIRT4 blocks glutamine metabolism, arrests the cell cycle and suppresses tumor formation.

The scientists tested this SIRT4 response in mice. Bred to lack the gene that encodes the SIRT4 protein but otherwise normal, the mice spontaneously developed lung cancer by 15 months.

"When SIRT4 is missing, you don't have this metabolic checkpoint involving glutamine, which is important because glutamine is an amino acid required for proliferation in the cell," Haigis said. "Without SIRT4, the cell keeps dividing even in the face of DNA damage, so the cell accumulates more damage."

The scientists also analyzed data showing SIRT4 gene expression levels are low in several human cancers, including small-cell lung carcinoma, gastric cancer, bladder carcinoma, breast cancer and leukemia.

While they cannot say if SIRT4 loss alone will initiate cancer, its absence appears to create an environment in which tumor cells survive and grow.

"Our findings suggest that SIRT4 may be a potential target against tumors," they conclude.


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Contact: David Cameron
david_cameron@hms.harvard.edu
617-432-0441
Harvard Medical School
Source:Eurekalert

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