Our body’s cells have these molecular tips called telomeres on the ends of chromosomes to protect them. They keep the chromosomes from fusing when the cells do their work of continually dividing and duplicating their DNA. These telomeres are like the plastic tips that protect the ends of shoelaces and keep them from fraying when we lace them onto shoes and tie them continuously. Although the result of losing the plastic tips on your laces vs the result of losing telomere is not the same – one leads to messy laces, the other leads to cancer.
Another thing that happens as this process occurs is that each time a cell copies its genetic material, it loses some details from the ends of each chromosome, this is similar to the way every photocopy of a copy becomes a little less crisp than the previous version. In other words, each time a cell duplicate their DNA to divide and grow, its telomeres get a little bit shorter.
Eventually, telomeres become so short that they can no longer effectively protect chromosomes. They eventually erode and expose vital genes to wear and tear, whereupon cells get a signal to stop dividing permanently, which causes a cell to die. That is a good thing. It is the natural process. If they do not die there will be problems… like cancer.
When cells don’t get the message and keep on dividing, it is due to cancer-causing viruses or other factors. When these cells don’t get the message to stop, and the telomeres are dangerously short, or missing, the cells enter a state called crisis.
Crisis is when the unprotected (without their telomeres) chromosomes can fuse and become dysfunctional — a hallmark of some cancers. Cancer cells (vs normal cells) are given a sort of immortality by these telomeres that are constantly rebuilding, even though they are in bad condition, and are suppose to die.
These researchers wanted to better understand crisis for two important reasons:
- Crisis often results in widespread cell death that prevents precancerous cells from continuing to full-blown cancer.
- The mechanism underlying this beneficial cell death isn’t well-understood.
This relationship of telomeres to cancer is what Salk Institute scientists were studying when they made a surprising discovery: a cellular recycling process called autophagy — generally thought of as a survival mechanism — actually promotes the death of cells (like apoptosis does but in a different way), thereby preventing cancer initiation. The research has been published in the journal Nature.
It reveals autophagy to be a completely novel tumor-suppressing pathway. Furthermore, it suggests that treatments to block the process of autophagy in an effort to curb cancer may unintentionally promote it very early on.
Jan Karlseder, a professor in Salk’s Molecular and Cell Biology Laboratory and the senior author of the paper, says:
“These results were a complete surprise. There are many checkpoints that prevent cells from dividing out of control and becoming cancerous, but we did not expect autophagy to be one of them.”
Joe Nassour, a postdoctoral fellow in the Karlseder lab and the paper’s first author, says:
“Many researchers assumed cell death in crisis occurs through apoptosis, which along with autophagy is one of two types of programmed cell death. But no one was doing experiments to find out if that was really the case.”
What they have discovered is contrary to what has been believed to be true – that this cellular recycling process (autophagy) fuels cancer growth. Their work reveals that, without autophagy, cells that lose other safety measures, such as tumor-suppressing genes, advance to a crisis state of unchecked growth, rampant DNA damage – and often cancer. Therefore, autophagy can actually prevent cancer.
Karlseder, who holds the Donald and Darlene Shiley Chair, adds:
“This work is exciting because it represents so many completely novel discoveries. We didn’t know it was possible for cells to survive crisis; we didn’t know autophagy is involved with the cell death in crisis; we certainly didn’t know how autophagy prevents the accumulation of genetic damage. This opens up a completely new field of research we are eager to pursue.”
Future research plans involve investigating the split in cell-death pathways. Why is it that damage to chromosome ends (telomeres) leads to autophagy while damage to other parts of chromosomes leads to apoptosis? They will also continue to studying telomeres themselves. They need to fully understand the complex ins and outs of a normal telomere function and regulation in order to understand it better when it is not behaving normally.
That knowledge will lead them to determine how to stop this telomere extension (make it so the chromosomes don’t fuse). Once they know how to do that, they may be able to make cancer cells die or render them more susceptible to drugs. Then, they’ll move on to learning how to make telomeres grow. If they can reverse the natural shrinking of these telomeres, then they could treat premature aging syndromes too.