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Updated: Aug 10, 2026

Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence
Published on: May 22, 2013
Telomere shortening and apoptosis in telomerase-inhibited human tumor cells
Abstract:
Despite a strong correlation between telomerase activity and malignancy, the outcome of telomerase inhibition in human tumor cells has not been examined. Here, we have addressed the role of telomerase activity in the proliferation of human tumor and immortal cells by inhibiting TERT function. Inducible dominant-negative mutants of hTERT dramatically reduced the level of endogenous telomerase activity in tumor cell lines. Clones with short telomeres continued to divide, then exhibited an increase in abnormal mitoses followed by massive apoptosis leading to the loss of the entire population. This cell death was telomere-length dependent, as cells with long telomeres were viable but exhibited telomere shortening at a rate similar to that of mortal cells. It appears that telomerase inhibition in cells with short telomeres lead to chromosomal damage, which in turn trigger apoptotic cell death. These results provide the first direct evidence that telomerase is required for the maintenance of human tumor and immortal cell viability, and suggest that tumors with short telomeres may be effectively and rapidly killed following telomerase inhibition.
Insights
Telomerase inhibition in human tumor cells with short telomeres triggers cell death. This study shows telomerase is essential for cancer cell survival, suggesting a targeted therapy approach.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Telomerase activity strongly correlates with malignancy.
- The impact of telomerase inhibition on human tumor cells remains largely unexamined.
Purpose of the Study:
- To investigate the role of telomerase activity in human tumor and immortal cell proliferation.
- To determine the outcome of inhibiting telomerase reverse transcriptase (TERT) function.
Main Methods:
- Utilized inducible dominant-negative mutants of hTERT to inhibit telomerase activity in tumor cell lines.
- Observed and analyzed cell division, mitosis, apoptosis, and telomere length in response to inhibition.
Main Results:
- Inhibition of hTERT significantly reduced endogenous telomerase activity.
- Cells with short telomeres underwent abnormal mitoses and massive apoptosis, leading to population loss.
- Cell death was dependent on telomere length; cells with long telomeres survived but showed telomere shortening.
Conclusions:
- Telomerase is essential for maintaining the viability of human tumor and immortal cells.
- Telomere shortening and subsequent chromosomal damage trigger apoptosis upon telomerase inhibition.
- Tumors with critically short telomeres represent a promising target for rapid eradication via telomerase inhibition.
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