Tumorogensis: The Dual Role of Telomerase

Carcinogenesis is a multistep process characterized by the gradual accumulation of genetic changes that ultimately lead to cancer. These genetic mutations can impart limitless replicative potential to the cancer cells making them immortal. Telomeres are repeat nucleotide sequence TTAGGG that are present at the end of chromosomes. Its functions are to protect the chromosomal ends and to ensure that these ends are not recognized as DNA strand break by the polymerase enzyme. They also act as a clock like mechanism to count the number of times a cell divides. These telomeres are maintained in the cell by an enzyme called as telomerase. The function of telomerase enzyme is to protect the cells from telomere erosion and senescence. Thus, the cell can become immortal and replicate forever. This is called as the canonical function of telomerase. Normally telomerase is present in stem cells, germ cells and blood cells only and the somatic cells usually do not express telomerase. However, a very high concentration of telomerase has been identified in various cancer cells. A few years back it was observed that low levels of telomerase are present in the S phase of cell cycle of somatic cells at levels that are not sufficient to maintain telomeres lengths. Additionally it was observed that ectopic expression of telomerase causes stem cell division, mobilization and migration, increased wound repair and an increased tumor burden. Based on these facts it has been deduced that telomerase has at least one non-canonical and elongation-independent function. Both canonical and non-canonical functions of telomerase are considered to play important roles in development and progression of tumorogensis.