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Epigenetic regulation of Smad2 and Smad3 by profilin-2 promotes lung cancer growth and metastasis

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  • Yun-Neng Tang

    (State Key Laboratory of Cell Biology, Innovation Center for Cell Signalling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Wei-Qiao Ding

    (State Key Laboratory of Cell Biology, Innovation Center for Cell Signalling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Xiao-Jie Guo

    (State Key Laboratory of Cell Biology, Innovation Center for Cell Signalling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Xin-Wang Yuan

    (State Key Laboratory of Cell Biology, Innovation Center for Cell Signalling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Dong-Mei Wang

    (State Key Laboratory of Cell Biology, Innovation Center for Cell Signalling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Jian-Guo Song

    (State Key Laboratory of Cell Biology, Innovation Center for Cell Signalling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

Abstract

Altered transforming growth factor-β (TGF-β) signalling has been implicated in tumour development and progression. However, the molecular mechanism behind this alteration is poorly understood. Here we show that profilin-2 (Pfn2) increases Smad2 and Smad3 expression via an epigenetic mechanism, and that profilin-2 and Smad expression correlate with an unfavourable prognosis of lung cancer patients. Profilin-2 overexpression promotes, whereas profilin-2 knockdown drastically reduces, lung cancer growth and metastasis. We show that profilin-2 suppresses the recruitment of HDAC1 to Smad2 and Smad3 promoters by preventing nuclear translocation of HDAC1 through protein–protein interaction at the C terminus of both proteins, leading to the transcriptional activation of Smad2 and Smad3. Increased Smad2 and Smad3 expression enhances TGF-β1-induced EMT and production of the angiogenic factors VEGF and CTGF. These findings reveal a new regulatory mechanism of TGF-β1/Smad signalling, and suggest a potential molecular target for the development of anticancer drugs.

Suggested Citation

  • Yun-Neng Tang & Wei-Qiao Ding & Xiao-Jie Guo & Xin-Wang Yuan & Dong-Mei Wang & Jian-Guo Song, 2015. "Epigenetic regulation of Smad2 and Smad3 by profilin-2 promotes lung cancer growth and metastasis," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9230
    DOI: 10.1038/ncomms9230
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    Cited by:

    1. Ravinder K. Bahia & Xiaoguang Hao & Rozina Hassam & Orsolya Cseh & Danielle A. Bozek & H. Artee Luchman & Samuel Weiss, 2023. "Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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