Nuclear translocation of PKM2/AMPK complex sustains cancer stem cell populations under glucose restriction stress
Journal
Cancer Letters
Journal Volume
421
Pages
28-40
Date Issued
2018
Author(s)
Yang Y.-C.
Chien M.-H.
Liu H.-Y.
Chang Y.-C.
Chen C.-K.
Lee W.-J.
Kuo T.-C.
Hsiao M.
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. ? 2018 Elsevier B.V.
SDGs
Other Subjects
hydroxymethylglutaryl coenzyme A reductase kinase; octamer transcription factor 4; pyruvate kinase; pyruvate kinase M2; unclassified drug; adenylate kinase; carrier protein; membrane protein; thyroid hormone; thyroid hormone-binding proteins; animal tissue; Article; cancer stem cell; cell population; cell survival; chromatin immunoprecipitation; controlled study; enzyme activation; glucose metabolism; glucose restriction stress; human; human cell; immunofluorescence; limit of quantitation; male; mouse; nonhuman; priority journal; protein expression; protein function; protein protein interaction; protein targeting; real time polymerase chain reaction; Western blotting; adaptation; animal; cancer stem cell; cell nucleus; metabolism; nonobese diabetic mouse; nucleocytoplasmic transport; physiological stress; physiology; SCID mouse; tumor cell line; xenograft; Active Transport, Cell Nucleus; Adaptation, Physiological; Adenylate Kinase; Animals; Carrier Proteins; Cell Line, Tumor; Cell Nucleus; Heterografts; Humans; Male; Membrane Proteins; Mice; Mice, Inbred NOD; Mice, SCID; Neoplastic Stem Cells; Stress, Physiological; Thyroid Hormones
Type
journal article