Evading cell death and replicating without limit: BCL2 and telomerase !
- Mechanism
Cancer cells switch off their own self-destruct programme and rebuild the ends of their chromosomes so they can divide forever.
Updated 2026-11-01
What it is
Normal cells with damaged DNA or lost signals die by apoptosis, and normal cells can divide only a limited number of times before short telomeres stop them. Cancer cells escape both limits: they disable the intrinsic (mitochondrial) apoptotic pathway, often by overexpressing BCL2 or losing p53, and they reactivate telomerase to maintain telomeres. Together these traits let a clone survive long enough to accumulate the rest of its mutations.
Function
- Escape from apoptosis gives time for further mutations and explains resistance to chemotherapy and radiation, which kill largely by triggering apoptosis.
- Loss of p53 and RB also lets cells bypass senescence, the permanent growth arrest of ageing cells.
- Telomere crisis before telomerase reactivation may cause chromosome fusions, a source of genomic instability.
Step by step
- DNA damage or growth factor withdrawal activates BH3-only sensor proteins.
- Sensors neutralise BCL2 and BCL-XL and free BAX and BAK.
- BAX and BAK form pores in the outer mitochondrial membrane; cytochrome c leaks out.
- Cytochrome c joins APAF1 in the apoptosome, which activates caspase 9 and then caspase 3.
- In cancer, extra BCL2 or absent p53 blocks this chain, so damaged cells survive.
- Each division shortens telomeres; very short telomeres normally trigger senescence or crisis.
- Cancer cells that switch on TERT keep their telomeres long and escape this limit.
Clinical notes
- Follicular lymphoma is usually indolent but hard to cure because its cells resist death.
- BCL2 inhibitors are used in chronic lymphocytic leukaemia and some acute myeloid leukaemias; rapid killing can cause tumour lysis syndrome.
- TERT promoter mutations are frequent in melanoma, glioblastoma and bladder cancer.
Test yourself
Think of the answer, then tap the question to see it.
What translocation overexpresses BCL2 and in which tumour?
t(14;18) between IGH and BCL2, characteristic of follicular lymphoma.
Why does follicular lymphoma grow slowly but resist cure?
Its cells accumulate because they fail to undergo apoptosis rather than because they divide fast.
Which enzyme lets cancer cells keep dividing indefinitely?
Telomerase (catalytic subunit TERT), which adds telomeric repeats to chromosome ends.
Which molecule released from mitochondria triggers the apoptosome?
Cytochrome c, which binds APAF1 and activates caspase 9.
Related
- Apoptosis: the intrinsic and extrinsic pathways
- The hallmarks of cancer
- Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis
- Cellular aging: telomeres, DNA damage, senescence and proteostasis
- Translocations, amplifications and epigenetic changes in cancer
- The cell cycle in cancer: cyclins, CDKs and checkpoints
Related conditions
- Non-Hodgkin lymphoma
- Chronic lymphocytic leukaemia
- Dyskeratosis congenita and other telomere biology disorders
- Lung cancer
- Melanoma
Elsewhere in DurgiPedia
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: TERT gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); TP53 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Targeted Therapy to Treat Cancer (National Cancer Institute (NCI), 2026).
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Representative model, for educational purposes only.