One of the characteristics of cancer cells is that they don’t die of old age. In a sense, they’re immortal – though of course they can be killed. The main reason for their longevity has been traced to telomeres a strip of non-coding genes at the ends of chromosomes. When normal cells replicate very often a piece of the telomere is lost, snipped off so to speak. Eventually the entire telomere is lost, which is sort of like losing the plastic caps on the ends of shoelaces that keeps them from unraveling. When the telomere is gone, the reproduction machinery gets no signal that it’s at the end of the chromosome, and it malfunctions. The cell dies (which is normal). With cancerous cells, however, telomeres are constantly lengthened and the cell goes on reproducing without end. (The so called ‘wild growth’ of cancer.)
Scientists have identified that the enzyme telomerase prevents the shortening of telomeres. Telomerase is always present in the cell, but its activity is kept in balance by a specific protein (called TRF1), which maintains telomere length. However, over time, another protein (Fbx4) binds itself to TRF1 and degrades it so that it can no longer stop telomerase activity and the telomeres lengthen. Fbx4 is the agent of cancer.
To stop Fbx4 from affecting cells, scientists at the University of Michigan Medical School have discovered a protein (TIN2) that prevents Fbx4 from attaching to TRF1. (Sorry about the alphabet soup of abbreviations, but the real names of proteins are forbidding.) Without all the ‘which protein did what to another protein’, the key here is that nearly all cancers create immortal telomeres; part of cancer’s uncontrolled growth is that old cancer cells don’t die. If scientists can figure out how to prevent Fbx4 from working, they may find a way to treat not just a particular cancer, or a variety of cancer – but all cancers. No doubt there are limitations to this ‘universal’ application; but the concept’s power is obvious.
“In 90 percent of cancers, no matter what caused the cancer to form, it needs telomerase activity to maintain the cell. Without telomerase, the cell will die. Our work is key to understanding a detailed mechanism for how these molecules interact and how to design a drug to block Fbx4,” says senior author Ming Lei, Ph.D., assistant professor of biological chemistry at the University of Michigan Medical School.
“If we find a drug that can inhibit telomerase activity in any fashion, that could be a universal cancer drug.”
[Source: University of Michigan Medical School]
As is usually the case when first published, this knowledge is only a step in the direction of finding actual medical applications. The researchers are looking for other substances (peptides) that can mimic TIN2, which could lead to a long series of pharmacological studies.
Note that telomerase activity is also at the center of a very rapidly growing body of research on aging. Scientists are also working on discovery of the processes and meaning of the gradual loss of telomeres as they affect cell longevity. There is considerable anticipation in the biomedical community that the various paths of telomere/telomerase research may lead to some very important applications in both cancer (oncology) and longer lives (gerontology).