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

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.
AuthorsYi-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
JournalCancer letters (Cancer Lett) Vol. 421 Pg. 28-40 (05 01 2018) ISSN: 1872-7980 [Electronic] Ireland
PMID29408265 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2018 Elsevier B.V. All rights reserved.
Chemical References
  • Carrier Proteins
  • Membrane Proteins
  • Thyroid Hormones
  • Adenylate Kinase
Topics
  • Active Transport, Cell Nucleus (physiology)
  • Adaptation, Physiological (physiology)
  • Adenylate Kinase (metabolism)
  • Animals
  • Carrier Proteins (metabolism)
  • Cell Line, Tumor
  • Cell Nucleus (metabolism)
  • Heterografts
  • Humans
  • Male
  • Membrane Proteins (metabolism)
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplastic Stem Cells (metabolism)
  • Stress, Physiological (physiology)
  • Thyroid Hormones (metabolism)
  • Thyroid Hormone-Binding Proteins

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