Nuclear translocation of PKM2/AMPK complex sustains cancer stem cell populations under glucose restriction stress

Yi Chieh Yang, Ming Hsien Chien, Hsin Yi Liu, Yu Chan Chang, Chi Kuan Chen, Wei Jiunn Lee, Tsang Chih Kuo, Michael Hsiao, Kuo Tai Hua, Tsu Yao Cheng

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Cancer cells encounter metabolic stresses such as hypoxia and nutrient limitations because they grow and divide more quickly than their normal counterparts. In response to glucose restriction, we found that nuclear translocation of the glycolic enzyme, pyruvate kinase M2 (PKM2), helped cancer cells survive under the metabolic stress. Restriction of glucose stimulated AMPK activation and resulted in co-translocation of AMPK and PKM2 through Ran-mediated nuclear transport. Nuclear PKM2 subsequently bound to Oct4 and promoted the expression of cancer stemness-related genes, which might enrich the cancer stem cell population under the metabolic stress. Nuclear PKM2 was also capable of promoting cancer metastasis in an orthotopic xenograft model. In summary, we found that cytosolic AMPK helped PKM2 carry out its nonmetabolic functions in the nucleus under glucose restriction and that nuclear PKM2 promoted cancer stemness and metastasis. These findings suggested a potential new targeting pathway for cancer therapy in the future.

Original languageEnglish
Pages (from-to)28-40
Number of pages13
JournalCancer Letters
Volume421
DOIs
Publication statusPublished - May 1 2018

Keywords

  • AMPK
  • Cancer stemness
  • Glucose restriction
  • Pyruvate kinase M2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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