Telomere Maintenance and Oncogenesis

An overwhelming majority of cancers exhibit telomere length reduction and differentiation markers consistent with a post-stem cell of origin. On the other hand, telomere shortening/damage is believed to protect cells from malignant transformation through induction of apoptosis. However, increased cancer incidence in the absence of apoptotic factors like p53 may suggest a favorable role of telomere shortening/damage in cancer development. Some findings suggest that telomere shortening may induce architectural changes in telomeric chromatin, such as those underlying the telomere position effect that support telomere maintenance of some tumors Here, we propose that several signaling pathways, in conjunction with telomere shortening/damage, may result in the release of Rap1 from telomeres. Its subsequent interaction with the embryonic stem cell marker Zscan4 may support immortalization and malignant transformation of the target cell.