Cited by 523Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsCancer-related Molecular Pathways

Role of telomeres and telomerase in cancer

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Shay, Jerry W., Wright, Woodring E.·2011·Seminars in Cancer Biology

Abstract

There is mounting evidence for the existence of an important relationship between telomeres and telomerase and cellular aging and cancer. Normal human cells progressively lose telomeres with each cell division until a few short telomeres become uncapped leading to a growth arrest known as replicative aging. In the absence of genomic alterations these cells do not die but remain quiescent producing a different constellation of proteins compared to young quiescent cells. Upon specific genetic and epigenetic alterations, normal human cells bypass replicative senescence and continue to proliferate until many telomere ends become uncapped leading to a phenomenon known as crisis. In crisis cells have critically shortened telomeres but continue to attempt to divide leading to significant cell death (apoptosis) and progressive genomic instability. Rarely, a human cell escapes crisis and these cells almost universally express the ribonucleoprotein, telomerase, and maintain stable but short telomeres. The activation of telomerase may be thought of as a mechanism to slow down the rate genomic instability due to dysfunctional telomeres. While telomerase does not drive the oncogenic process, it is permissive and required for the sustain growth of most advanced cancers. Since telomerase is not expressed in most normal human cells, this has led to the development of targeted telomerase cancer therapeutic approaches that are presently in advanced clinical trials.

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Authors
Shay, J. W., & Wright, W. E.
Affiliations
The University of Texas Southwestern Medical Center (US)
Corresponding author
Shay, Jerry W.
Venue
Seminars in Cancer Biology
Publisher
Elsevier BV
Published
2011-12
Volume
21
Issue
6
Pages
349-353
ISSN
1044-579X (ISSN-L)
OpenAlex
W2095900421
Cited by
523
References
33
Citations by year
2026: 19 · 2025: 24 · 2024: 19 · 2023: 21 · 2022: 24 · 2021: 37 · 2020: 40 · 2019: 53 · 2018: 58 · 2017: 39 · 2016: 30 · 2015: 42 · 2014: 42 · 2013: 52 · 2012: 21
FWCI
3.97
Type
journal article
Language
en
Open access
Locations
  • Seminars in Cancer Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (P50CA070907, T32CA124334)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
telomeres, telomerase, cancer, cellular aging, replicative senescence, genomic instability, apoptosis, telomere uncapping
MeSH terms
Humans, Neoplasms, Neoplastic Stem Cells, Telomere, Telomerase

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