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 journalArticlepeer-review

    54 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

    Bibliographical note

    Funding Information:
    This work was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea. (A080098). X.J. was supported by a BK21 Research Fellowship from the Ministry of Education and Human Resources Development. S.H.K was supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF-2009-351 -C001 37).

    Keywords

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

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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