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Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression

Author

Listed:
  • Youhua Tan

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology
    College of Engineering, University of Illinois at Urbana–Champaign)

  • Arash Tajik

    (College of Engineering, University of Illinois at Urbana–Champaign)

  • Junwei Chen

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Qiong Jia

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Farhan Chowdhury

    (Institute for Genomic Biology, University of Illinois at Urbana–Champaign)

  • Lili Wang

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Junjian Chen

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Shuang Zhang

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Ying Hong

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Haiying Yi

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Douglas C. Wu

    (College of Engineering, University of Illinois at Urbana–Champaign)

  • Yuejin Zhang

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Fuxiang Wei

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Yeh-Chuin Poh

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology
    College of Engineering, University of Illinois at Urbana–Champaign)

  • Jihye Seong

    (College of Engineering, University of Illinois at Urbana–Champaign
    University of Illinois at Urbana–Champaign
    Present address: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, South Korea)

  • Rishi Singh

    (College of Engineering, University of Illinois at Urbana–Champaign)

  • Li-Jung Lin

    (University of Illinois at Urbana–Champaign)

  • Sultan Doğanay

    (Institute for Genomic Biology, University of Illinois at Urbana–Champaign
    Center for Biophysics and Computational Biology and Center for the Physics of Living Cells, University of Illinois at Urbana–Champaign, Howard Hughs Medical Institute)

  • Yong Li

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Haibo Jia

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Taekjip Ha

    (Institute for Genomic Biology, University of Illinois at Urbana–Champaign
    Center for Biophysics and Computational Biology and Center for the Physics of Living Cells, University of Illinois at Urbana–Champaign, Howard Hughs Medical Institute)

  • Yingxiao Wang

    (University of California–San Diego)

  • Bo Huang

    (Tongji Medical College, Huazhong University of Science and Technology
    Institute of Basic Medical Sciences of Chinese Academy of Medical Sciences)

  • Ning Wang

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology
    College of Engineering, University of Illinois at Urbana–Champaign)

Abstract

Tumour-repopulating cells (TRCs) are a self-renewing, tumorigenic subpopulation of cancer cells critical in cancer progression. However, the underlying mechanisms of how TRCs maintain their self-renewing capability remain elusive. Here we show that relatively undifferentiated melanoma TRCs exhibit plasticity in Cdc42-mediated mechanical stiffening, histone 3 lysine residue 9 (H3K9) methylation, Sox2 expression and self-renewal capability. In contrast to differentiated melanoma cells, TRCs have a low level of H3K9 methylation that is unresponsive to matrix stiffness or applied forces. Silencing H3K9 methyltransferase G9a or SUV39h1 elevates the self-renewal capability of differentiated melanoma cells in a Sox2-dependent manner. Mechanistically, H3K9 methylation at the Sox2 promoter region inhibits Sox2 expression that is essential in maintaining self-renewal and tumorigenicity of TRCs both in vitro and in vivo. Taken together, our data suggest that 3D soft-fibrin-matrix-mediated cell softening, H3K9 demethylation and Sox2 gene expression are essential in regulating TRC self-renewal.

Suggested Citation

  • Youhua Tan & Arash Tajik & Junwei Chen & Qiong Jia & Farhan Chowdhury & Lili Wang & Junjian Chen & Shuang Zhang & Ying Hong & Haiying Yi & Douglas C. Wu & Yuejin Zhang & Fuxiang Wei & Yeh-Chuin Poh & , 2014. "Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5619
    DOI: 10.1038/ncomms5619
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