Role of telomeres and telomerase in cancer

Jerry W. Shay, Woodring E. Wright

Research output: Contribution to journalArticle

283 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)349-353
Number of pages5
JournalSeminars in Cancer Biology
Volume21
Issue number6
DOIs
StatePublished - Dec 2011

Fingerprint

Telomerase
Telomere
Neoplasms
Genomic Instability
Cell Aging
Telomere Shortening
Ribonucleoproteins
Growth
Epigenomics
Cell Division
Cell Death
Clinical Trials
Apoptosis

Keywords

  • Aging
  • DNA damage
  • Evolutionary considerations
  • Immortalization
  • Replicative senescence
  • Stem cells

ASJC Scopus subject areas

  • Cancer Research

Cite this

Role of telomeres and telomerase in cancer. / Shay, Jerry W.; Wright, Woodring E.

In: Seminars in Cancer Biology, Vol. 21, No. 6, 12.2011, p. 349-353.

Research output: Contribution to journalArticle

Shay, Jerry W. ; Wright, Woodring E. / Role of telomeres and telomerase in cancer. In: Seminars in Cancer Biology. 2011 ; Vol. 21, No. 6. pp. 349-353.
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