AMP-activated protein kinase regulates the expression of human telomerase reverse transcriptase

Daum Jo, Rackhyun Park, Hyunju Kim, Minsu Jang, Eun Ju Lee, Ik Soon Jang, Junsoo Park

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The expression of hTERT in tumor cells contributes to oncogenic transformation by promoting immortalization. For this reason, hTERT is one of the major targets for cancer therapy, and an efficient method to downregulate hTERT expression is required for treatment of hTERT-positive cancer. In this report, we demonstrated that inhibition of AMP-activated protein kinase (AMPK) downregulates the expression of hTERT. We screened cell signaling pathways in AMPK α1 knockout cells and found that AMPKα1 is required for activity of the hTERT promoter. AMPKα1 knockout cells showed decreased expression of hTERT mRNA and protein. We also demonstrated that compound C, a reversible AMPK inhibitor, suppressed the expression of hTERT. However, AMPK activators, including AICAR and metformin, did not increase the level of hTERT protein. Finally, we showed that tumor cells stably expressing hTERT are resistant to compound C treatment. These results indicate that AMPK activity is required for tumor progression.

Original languageEnglish
Article numbere0207864
JournalPloS one
Volume13
Issue number11
DOIs
Publication statusPublished - 2018 Nov

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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