Telomeres and cancer

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DD
DD's picture
Telomeres and cancer

I need some insights regarding the role of the telomeres and cancer. In the process of fighting aging cells, it has been argued that longer telomeres are indications of the cell longevity. On the other hand a cell longevity can later on leads into cell immortality and cancer. Does anyone know how the balance between cells living longer and telomere health is kept without promoting the occurance of malignancies?

samm
samm's picture
Longetivity and the

Longetivity and the uncontrolled proliferation that leads to malignancies are often two entirely separate processes, though as you point out, some molecular pathways intersect.
Telomeres essentially get around the "end-replication" problem, losing a bit of their own substance in the process. This essentially serves as a time out clock, limiting the total number of replication cycles that cell can undergo.
Enhanced telomerase activity - often seen in cells "immortalized" in vitro - can help conserve telomere length, preventing damage to the crucial gene-coding regions near the ends of the chromosomes (there seems to be a bias to that - probably yet another regulatory mechanism).
On the other hand, the uncontrolled proliferation in cancers arise from a variety of factors, both genetic and environmental, including assorted growth factors, viruses etc. There are also many checkpoints - at the level of metabolism, cell proliferation, angiogenesis and metastasis, that help keep cancers in check - in fact, it has been suggested that most individuals bear a number of miniscule "tumors" in their bodies, which never progress to anything more!
This subject has been covered in publications ranging from Scientific American to Current Biology/Mol Cell and Nature Rev Med among others - you can do a search to get both general and specific info from these sources.

labrat
labrat's picture
DD - telomeres are used by

DD - telomeres are used by the cell as a counting mechanism of the number of divisions a cell has passed through. You are right in thinking that the longer a cell lives, the more chance it has of collecting cancer related mutations. However, it is thought that the point at which most cancer related changes occur is when the cell goes through a phase called crisis.

This occurs when the telomeres of a cell are critically short and they are incorrectly recognised by the cell as dna damage. At this point, dna damage repair mechanisms can join chromosome ends together. This causes all sorts of problems when cells try to divide and causes cellular crisis. At this stage, most cells die because the chromosomes have huge amounts of genetic changes due to the chromosomes being pulled apart during cell division. Occasionally though, these changes will cause the activation of telomere maintenance - either by activation of telomerase, or through recombination pathways (ALT mechanism). These changes can also include alterations to genes involved in cancer - such as proliferation, invasion etc. This leads to an immortal cell with malignant tendencies.

So the effects that occur at crisis are independent of the age of the cell and the length of telomeres the cell had to begin with.

A cell becoming malignant is actually an extremely rare event. I know that in the scales we consider - i.e. occurances per head of population - it is common, but if you think of how many cells there are in a human body, and the fact that it's extremely rare for a person to get more than one cancer independtly (i.e. not metastasised from the first or a recurrance of the original cancer).

And as far as evolution and natural selection is concerned, cancer is fairly irrelevant, since it usually occurs after reproduction - unless you consider that survival age of parents can effect survival chances of the offspring which is a whole other story!

What is your interest in the topic?