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Integrated analysis of telomerase enzymatic activity unravels an association with cancer stemness and proliferation

Author

Listed:
  • Nighat Noureen

    (UT Health San Antonio
    UT Health San Antonio)

  • Shaofang Wu

    (MD Anderson Cancer Center)

  • Yingli Lv

    (UT Health San Antonio)

  • Juechen Yang

    (UT Health San Antonio)

  • W. K. Alfred Yung

    (MD Anderson Cancer Center)

  • Jonathan Gelfond

    (UT Health San Antonio)

  • Xiaojing Wang

    (UT Health San Antonio
    UT Health San Antonio)

  • Dimpy Koul

    (MD Anderson Cancer Center)

  • Andrew Ludlow

    (University of Michigan)

  • Siyuan Zheng

    (UT Health San Antonio
    UT Health San Antonio)

Abstract

Active telomerase is essential for stem cells and most cancers to maintain telomeres. The enzymatic activity of telomerase is related but not equivalent to the expression of TERT, the catalytic subunit of the complex. Here we show that telomerase enzymatic activity can be robustly estimated from the expression of a 13-gene signature. We demonstrate the validity of the expression-based approach, named EXTEND, using cell lines, cancer samples, and non-neoplastic samples. When applied to over 9,000 tumors and single cells, we find a strong correlation between telomerase activity and cancer stemness. This correlation is largely driven by a small population of proliferating cancer cells that exhibits both high telomerase activity and cancer stemness. This study establishes a computational framework for quantifying telomerase enzymatic activity and provides new insights into the relationships among telomerase, cancer proliferation, and stemness.

Suggested Citation

  • Nighat Noureen & Shaofang Wu & Yingli Lv & Juechen Yang & W. K. Alfred Yung & Jonathan Gelfond & Xiaojing Wang & Dimpy Koul & Andrew Ludlow & Siyuan Zheng, 2021. "Integrated analysis of telomerase enzymatic activity unravels an association with cancer stemness and proliferation," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20474-9
    DOI: 10.1038/s41467-020-20474-9
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    Cited by:

    1. Funan He & Abhik M. Bandyopadhyay & Laura J. Klesse & Anna Rogojina & Sang H. Chun & Erin Butler & Taylor Hartshorne & Trevor Holland & Dawn Garcia & Korri Weldon & Luz-Nereida Perez Prado & Anne-Mari, 2023. "Genomic profiling of subcutaneous patient-derived xenografts reveals immune constraints on tumor evolution in childhood solid cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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