Telomerase activity-independent function of TERT allows glioma cells to attain cancer stem cell characteristics by inducing EGFR expression

Samuel Beck, Xun Jin, Young Woo Sohn, Jun Kyum Kim, Sung Hak Kim, Jinlong Yin, Xumin Pian, Sung Chan Kim, Do Hyun Nam, Yun Jaie Choi, Hyunggee Kim

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Telomerase reverse transcriptase (TERT), the catalytic subunit of the enzyme telomerase, is robustly expressed in cancer cells. TERT enables cells to avoid chromosome shortening during repeated replication by maintaining telomere length. However, several lines of evidence indicate that many cancer cells exhibit shorter telomere length than normal tissues, implying an additional function of TERT in tumor formation and progression. Here, we report a telomerase activity-independent function of TERT that induces cancer stemness in glioma cells. Overexpression of TERT712, a telomerase activity-deficient form of TERT, in U87MG cells promoted cell self-renewal in vitro, and induced EGFR expression and formation of gliomas exhibiting cellular heterogeneity in vivo. In patients with glioblastoma multiforme, TERT expression showed a high correlation with EGFR expression, which is closely linked to the stemness gene signature. Induction of differentiation and TERT-knockdown in glioma stem cells led to a marked reduction in EGFR expression, cancer stemness, and anticancer drug resistance. Together, our findings indicate that TERT plays a crucial role in tumor progression by promoting cancer stemness through expression of EGFR.

Original languageEnglish
Pages (from-to)9-15
Number of pages7
JournalMolecules and Cells
Volume31
Issue number1
DOIs
Publication statusPublished - 2011 Jan 1

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Neoplastic Stem Cells
Telomerase
Glioma
Neoplasms
Telomere
Glioblastoma
Drug Resistance
Stem Cells
Chromosomes

Keywords

  • bFGF
  • EGFR
  • Glioblastoma multiforme
  • Glioma stem cells
  • Telomerase

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Telomerase activity-independent function of TERT allows glioma cells to attain cancer stem cell characteristics by inducing EGFR expression. / Beck, Samuel; Jin, Xun; Sohn, Young Woo; Kim, Jun Kyum; Kim, Sung Hak; Yin, Jinlong; Pian, Xumin; Kim, Sung Chan; Nam, Do Hyun; Choi, Yun Jaie; Kim, Hyunggee.

In: Molecules and Cells, Vol. 31, No. 1, 01.01.2011, p. 9-15.

Research output: Contribution to journalArticle

Beck, Samuel ; Jin, Xun ; Sohn, Young Woo ; Kim, Jun Kyum ; Kim, Sung Hak ; Yin, Jinlong ; Pian, Xumin ; Kim, Sung Chan ; Nam, Do Hyun ; Choi, Yun Jaie ; Kim, Hyunggee. / Telomerase activity-independent function of TERT allows glioma cells to attain cancer stem cell characteristics by inducing EGFR expression. In: Molecules and Cells. 2011 ; Vol. 31, No. 1. pp. 9-15.
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