Figure 7.

Model illustrating the role of TDIS in suppressing malignant cancer progression in humans. Cells encountering oncogenic signals are exposed to telomeric replication stress, which leads to stochastic telomere attrition and telomere dysfunction in cells that lack telomerase activity. In normal somatic cells, telomere dysfunction results in cellular senescence, thereby preventing malignant cancer progression. In contrast, telomere dysfunction is suppressed in cells with high telomerase activity allowing these cells to continue proliferating. Similarly, in cells with compromised senescence responses, telomere dysfunction generates chromosomal instability, an event that is associated with reactivation of telomerase and malignant cancer progression.