Hallmarks of Cancer: Becoming Immortal

Cells have a lifespan. The age of a cell and its ability to divide is relatedto structures – telomeres – found at the ends of chromosomes.

Robert Weinberg, Ph.D
Whitehead Institute for Biomedic Research

Normal cells can only double a certain limited finite number of times; cancercells have to learn how to proliferate indefinitely, that i.e, they have to becomeimmortalized.

The machinery for controlling how often a cell may grow and divide, how manygenerations a lineage of cells may pass through, is carried in the telomericDNAs at the ends of chromosomes.



The telomeres are specialized sequences at the ends of each chromosome and theyoperate to prevent end-to-end fusion of chromosomes. These telomeres protectthe ends of chromosomal DNA from such accidents.

And as was learned in a number of laboratories when normal cells go through cyclesof growth and division their telomeric DNA gets shorter and shorter and shorterand ultimately so short it can no longer protect the ends of chromosomal DNA.

Telomeres start fusing. Chromosomes start fusing in those cells, and those cellsdie.

Cancer cells must avoid that problem because they want to grow indefinitely,and what do they do? They turn on an enzyme called telomerase that is normallyexpressed only early in embryologic development and in a small number of so-calledstem cells in the body.

The telomerase enzyme is able to extend the telomeres, making them longer andlonger thereby enabling the cancer cell to go through many, many cycles of growthand division without worrying about the imminent collapse of its telomeres. Thetelomerase ensures the telomeres stay very long.

In 2000, Douglas Hanahan (shown below) and Robert Weinberg published a paperin Cell, "The Hallmarks of Cancer," which identified some organizingprinciples of cancer cell development.

The nature of the replication machinery is that chromosomes get smaller everytime they divide. And we now appreciate that specialized cells in the body havea way to counteract this telomere shorting and that’s using several strategiesof which the most prominent is an enzyme known as telomerase that protects theends of chromosomes from this erosion.