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Pathology
Cancer Cells' Immortality May Depend on Longevity Protein
One of the hallmarks of a cancer cell is its ability to relentlessly divide without regard for the laws of mortality that govern nearly every other cell in the body. But in their early stages, even tumor cells obey—they undergo a limited number of cell divisions and then die. Eventually, a handful of cells, or possibly only one, finds a way to break through this barrier and give rise to a malignant mass.
David Sinclair (left) and Haim Cohen have identified a gene that some cancer cells may use to retain telomeres, and thus become immortal. People with a defective copy of the gene age prematurely, presumably due to a lack of telomeres. Photo by Pam Murray
A team of HMS researchers has identified a protein that 10 percent of tumor cells use to attain this immortal state. By blocking the molecule, it may be possible to stop these cancer cells from proliferating.
"This gives us a new drug target for cancer," said David Sinclair, HMS assistant professor of pathology. He and Haim Cohen, HMS research fellow in pathology, published their findings in the March 6 Proceedings of the National Academy of Sciences Early Edition.
Most tumor cells become cancerous by turning on a gene for telomerase, a protein that makes the protective caps at each end of a chromosome. In normal cells, these caps, or telomeres, erode every time a cell divides, and it is their steady unraveling that causes a cell to age and die.
But a minority of cancer cells—about 10 percent—manage to rebuild their telomeres without turning on the telomerase gene. Sinclair and his colleagues have evidence that they may be doing this by coopting the WRN protein, which is thought to build telomeres.
The researchers found that "humanized" yeast cells—whose telomerase gene is turned off—did not survive beyond the normal number of cell divisions when deprived of their version of the WRN gene, called SGS1. Yeast cell colonies endowed with SGS1 were able to proliferate endlessly.
If the WRN protein plays the same role in the 10 percent of human cancer cells that multiply without turning on telomerase, the discovery could lead to a new tumor-fighting strategy aimed at both protein pathways.
—Misia Landau
Copyright 2001 by the President and Fellows of Harvard College
