Telomeres and Cancer: Resolving the Paradox

Decades of study on cell cycle regulation have provided great insight into human cellular life span barriers, as well as their dysregulation during tumorigenesis. Telomeres, the extremities of linear chromosomes, perform an essential role in implementing these proliferative boundaries and preventing the propagation of potentially cancerous cells. The tumor-suppressive function of telomeres relies on their ability to initiate DNA damage signaling pathways and downstream cellular events, ranging from cell cycle perturbation to inflammation and cell death. While the tumor-suppressor role of telomeres is undoubtable, recent advances have pointed to telomeres as a major source of many of the genomic aberrations found in both early- and late-stage cancers, including the most recently discovered mutational phenomenon of chromothripsis. Telomere shortening appears as a double-edged sword that can function in opposing directions in carcinogenesis. This review focuses on the current knowledge of the dual role of telomeres in cancer and suggests a new perspective to reconcile the paradox of telomeres and their implications in cancer etiology.