Lin28/let-7 axis regulates aerobic glycolysis and cancer progression via PDK1

Xiaoyu Ma, Chenchen Li, Linchong Sun, Huang De, Tingting Li, Xiaoping He, Gongwei Wu, Zheng Yang, Xiuying Zhong, Libing Song, Ping Gao () and Huafeng Zhang ()
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Xiaoyu Ma: Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Science, University of Science and Technology of China
Chenchen Li: Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Science, University of Science and Technology of China
Linchong Sun: Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Science, University of Science and Technology of China
Huang De: Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Science, University of Science and Technology of China
Tingting Li: Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Science, University of Science and Technology of China
Xiaoping He: Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Science, University of Science and Technology of China
Gongwei Wu: Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Science, University of Science and Technology of China
Zheng Yang: Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Science, University of Science and Technology of China
Xiuying Zhong: Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Science, University of Science and Technology of China
Libing Song: Sun Yat-sen University Cancer Center
Ping Gao: Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Science, University of Science and Technology of China
Huafeng Zhang: Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Science, University of Science and Technology of China

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract Aberrant expression of Lin28 and let-7 has been observed in many human malignancies. However, its functions and underlying mechanisms remain largely elusive. Here we show that aberrant expression of Lin28 and let-7 facilitates aerobic glycolysis, or Warburg effect, in cancer cells. Mechanistically, we discover that Lin28A and Lin28B enhance, whereas let-7 suppresses, aerobic glycolysis via targeting pyruvate dehydrogenase kinase 1, or PDK1, in a hypoxia- or hypoxia-inducible factor-1 (HIF-1)-independent manner, illustrating a novel pathway to mediate aerobic glycolysis of cancer cells even in ambient oxygen levels. Importantly, we further demonstrate that PDK1 is critical for Lin28A- and Lin28B-mediated cancer proliferation both in vitro and in vivo, establishing a previously unappreciated mechanism by which Lin28/let-7 axis facilitates Warburg effect to promote cancer progression. Our findings suggest a potential rationale to target PDK1 for cancer therapy in malignancies with aberrant expression of Lin28 and let-7.

Date: 2014
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DOI: 10.1038/ncomms6212

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