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| Salk Institute scientist Jan Karlseder in the lab |
Yes, you read that right: stunt cancer cell growth. Their remarkable findings on something called telomeres, which are the stretches of DNA at the ends of chromosomes that protect our genetic code and make it possible for cells to divide, suggest a potential target for preventive measures against cancer, as well as aging.
Needless to say, the implications of this research for patients are potentially profound. The findings were published July 11 in Molecular Cell.
Karlseder, a professor in Salk’s Molecular and Cell Biology Laboratory and holder of the Donald and Darlene Shiley Chair, says that while these discoveries do not result in direct clinical applications, "the more we understand the underlying causes of cancer, the more likely it is that improved therapies will be developed. Understanding the exact molecular details of how partially dysfunctional telomeres arrest cell growth while maintaining genome stability could eventually allow the application of these pathways to cancer cells, thereby arresting their growth."
As usual, the research gets a little technical. Karlseder explains that telomeres are like plastic tips at the end of shoelaces because they prevent the ends of chromosomes from fraying and sticking to each other, which scrambles the genetic information and may promote cancer. They're crucial to DNA replication, tumor suppression and aging. Each time a human cell divides, its telomeres become shorter.
Needless to say, the implications of this research for patients are potentially profound. The findings were published July 11 in Molecular Cell.
Karlseder, a professor in Salk’s Molecular and Cell Biology Laboratory and holder of the Donald and Darlene Shiley Chair, says that while these discoveries do not result in direct clinical applications, "the more we understand the underlying causes of cancer, the more likely it is that improved therapies will be developed. Understanding the exact molecular details of how partially dysfunctional telomeres arrest cell growth while maintaining genome stability could eventually allow the application of these pathways to cancer cells, thereby arresting their growth."
As usual, the research gets a little technical. Karlseder explains that telomeres are like plastic tips at the end of shoelaces because they prevent the ends of chromosomes from fraying and sticking to each other, which scrambles the genetic information and may promote cancer. They're crucial to DNA replication, tumor suppression and aging. Each time a human cell divides, its telomeres become shorter.
When they become too short, he says, the cell can no longer divide and becomes inactive, or “senescent,” or dies. Cells can escape this fate by activating an enzyme called telomerase, which prevents telomeres from getting shorter and allows the cells to continue to grow and divide.
Uncontrolled cellular growth is of course a primary and scary hallmark of cancer cells, and shortened telomeres have been identified in pancreatic, bone, prostate, bladder, lung, kidney and head and neck cancers.
“As telomeres shorten during normal cellular aging, they activate a DNA damage response to arrest cell growth, which protects our DNA from harm,” says Karlseder, who with his team identified that cell growth arrest due to shortening telomeres is confined to one specific portion of the cell cycle, called the G1 phase, which is the most protected stage of the cell cycle.
Uncontrolled cellular growth is of course a primary and scary hallmark of cancer cells, and shortened telomeres have been identified in pancreatic, bone, prostate, bladder, lung, kidney and head and neck cancers.
“As telomeres shorten during normal cellular aging, they activate a DNA damage response to arrest cell growth, which protects our DNA from harm,” says Karlseder, who with his team identified that cell growth arrest due to shortening telomeres is confined to one specific portion of the cell cycle, called the G1 phase, which is the most protected stage of the cell cycle.
“The pathways controlling G1-phase growth arrest, however, is commonly altered in cancer cells," he says, "allowing cancer cells to divide despite shortened telomeres, which can lead to the genomic instability seen in malignant cells.”
In the study, Karlseder and his colleagues mimicked the process of cellular aging by partially removing a protein called TRF2 from the telomeres of human fibrosarcoma (a type of cancer that affects connective tissue) cells. By doing so they were able to experimentally reproduce the process that occurs naturally as cells age.
This telomere so-called “deprotection” exposed the ends of chromosomes during certain stages of the cell cycle.
This telomere so-called “deprotection” exposed the ends of chromosomes during certain stages of the cell cycle.
In this state, the scientists found that telomeres exhibited a partial DNA damage response: the ends of chromosomes were protected against fusing and fraying, but cell growth was still arrested.
“Basically,” notes lead author Anthony Cesare, a research associate in Karlseder’s lab, “there’s cell growth arrest without genomic instability. Thus, telomere aging, in normal, healthy cells and living organisms, means cell arrest, but no harmful genetic effects.”
As you might have guessed, I'm keeping a close eye on this promising research and will keep you informed.
As you might have guessed, I'm keeping a close eye on this promising research and will keep you informed.
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