The regulation of telomerase activity in human cells plays a significant role in the development of cancer. Telomerase is tightly repressed in the vast majority of normal human somatic cells but becomes activated during cellular immortalization and in cancers.
How is telomerase active in cancer?
Cancer cells often avoid senescence or cell death by maintaining their telomeres despite repeated cell divisions. This is possible because the cancer cells activate an enzyme called telomerase, which adds genetic units onto the telomeres to prevent them from shortening to the point of causing senescence or cell death.
How does telomerase get activated?
Telomerase activity can be induced in primary human keratinocytes and mammary epithelial cells by human papillomavirus 16 E6 protein (126). This activation is mediated by upregulation of hTERT transcription by E6, independent of degradation of p53 or induction of c-myc (75, 187, 238).
What happens to telomeres in cancer?
Telomeres, the protective structures of chromosome ends are gradually shortened by each cell division, eventually leading to senescence or apoptosis. Cancer cells maintain the telomere length for unlimited growth by telomerase reactivation or a recombination-based mechanism.
How does an increase in activated telomerase lead to cancer?
If a genetic mishap inadvertently turns telomerase production on, it can cause abnormal cells to multiply and form tumors. It is believed that as life expectancy rates continue to grow, the chances of this occur will not only become greater but eventually become inevitable.
Do cancer cells lack telomerase activity?
Most human cancers have short telomeres and express high levels of telomerase, whereas in most normal somatic tissues telomerase is absent (35,36).
What is the role of telomerase in aging and cancer?
The telomerase enables cancer cells to grow quickly and replicate indefinitely by keeping the telomeres long. Without telomerase, cancer cells would be deactivated, stop dividing and eventually undergo apoptosis.
What cells is telomerase active in?
Telomerase is found in fetal tissues, adult germ cells, and also tumor cells. Telomerase activity is regulated during development and has a very low, almost undetectable activity in somatic (body) cells.
Is telomerase active in stem cells?
In embryonic stem cells, telomerase is activated and maintains telomere length and cellular immortality; however, the level of telomerase activity is low or absent in the majority of stem cells regardless of their proliferative capacity.
Why is telomerase not active in somatic cells?
Telomerase activity is absent in most normal human somatic cells because of the lack of expression of TERT; TERC is usually present. … The absence of telomerase activity in most human somatic cells results in telomere shortening during aging.
Why do cancer cells have increased telomerase activity?
Some of the cells avoid crisis and activate the telomerase gene, telomerase reverse transcriptase (TERT), which codes for telomerase, the enzyme responsible for the synthesis of telomere. Telomerase activity allows the cancer cell to have unlimited replication.
Do cancer cells express more telomerase?
Telomerase is commonly expressed in human cancer cells. Increased telomerase expression produces vulnerability of cancer cells, distinguishing them from normal cells in the body, although normal cells do also have some active telomerase.
How can telomerase be targeted as a cancer treatment?
Approaches to targeting telomerase include: (1) Immunotherapies—peptide or DNA vaccines supply immunogenic TERT epitopes that stimulate immune responses against telomerase-expressing cancer cells. Adoptive cell transfer therapies entail the infusion of telomerase-specific cytotoxic T cells.
Does telomerase increase risk of cancer?
Long telomere–associated SNPs increase cancer risk
Although the role of germline telomerase and shelterin mutations in familial cancer may at first appear limited to small subsets of cancer patients, there is epidemiologic evidence supporting long telomere length itself as being associated with cancer risk.