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The SWI/SNF chromatin remodeling factor DPF3 regulates metastasis of ccRCC by modulating TGF-β signaling

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  • Huanhuan Cui

    (Southern University of Science and Technology
    Southern University of Science and Technology
    Southern University of Science and Technology)

  • Hongyang Yi

    (Southern University of Science and Technology)

  • Hongyu Bao

    (Southern University of Science and Technology
    Southern University of Science and Technology)

  • Ying Tan

    (Southern University of Science and Technology)

  • Chi Tian

    (Southern University of Science and Technology)

  • Xinyao Shi

    (Southern University of Science and Technology)

  • Diwen Gan

    (Southern University of Science and Technology)

  • Bin Zhang

    (King Abdullah University of Science and Technology (KAUST))

  • Weizheng Liang

    (Southern University of Science and Technology)

  • Rui Chen

    (Southern University of Science and Technology)

  • Qionghua Zhu

    (Southern University of Science and Technology
    Southern University of Science and Technology)

  • Liang Fang

    (Southern University of Science and Technology
    Southern University of Science and Technology
    Southern University of Science and Technology)

  • Xin Gao

    (King Abdullah University of Science and Technology (KAUST))

  • Hongda Huang

    (Southern University of Science and Technology
    Southern University of Science and Technology)

  • Ruijun Tian

    (Southern University of Science and Technology)

  • Silke R. Sperling

    (Charité-Universitätsmedizin Berlin)

  • Yuhui Hu

    (Southern University of Science and Technology
    Southern University of Science and Technology)

  • Wei Chen

    (Southern University of Science and Technology
    Southern University of Science and Technology
    Southern University of Science and Technology)

Abstract

DPF3, a component of the SWI/SNF chromatin remodeling complex, has been associated with clear cell renal cell carcinoma (ccRCC) in a genome-wide association study. However, the functional role of DPF3 in ccRCC development and progression remains unknown. In this study, we demonstrate that DPF3a, the short isoform of DPF3, promotes kidney cancer cell migration both in vitro and in vivo, consistent with the clinical observation that DPF3a is significantly upregulated in ccRCC patients with metastases. Mechanistically, DPF3a specifically interacts with SNIP1, via which it forms a complex with SMAD4 and p300 histone acetyltransferase (HAT), the major transcriptional regulators of TGF-β signaling pathway. Moreover, the binding of DPF3a releases the repressive effect of SNIP1 on p300 HAT activity, leading to the increase in local histone acetylation and the activation of cell movement related genes. Overall, our findings reveal a metastasis-promoting function of DPF3, and further establish the link between SWI/SNF components and ccRCC.

Suggested Citation

  • Huanhuan Cui & Hongyang Yi & Hongyu Bao & Ying Tan & Chi Tian & Xinyao Shi & Diwen Gan & Bin Zhang & Weizheng Liang & Rui Chen & Qionghua Zhu & Liang Fang & Xin Gao & Hongda Huang & Ruijun Tian & Silk, 2022. "The SWI/SNF chromatin remodeling factor DPF3 regulates metastasis of ccRCC by modulating TGF-β signaling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32472-0
    DOI: 10.1038/s41467-022-32472-0
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    References listed on IDEAS

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    1. Annika Fendler & Daniel Bauer & Jonas Busch & Klaus Jung & Annika Wulf-Goldenberg & Severine Kunz & Kun Song & Adam Myszczyszyn & Sefer Elezkurtaj & Bettina Erguen & Simone Jung & Wei Chen & Walter Bi, 2020. "Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    2. Lei Zeng & Qiang Zhang & SiDe Li & Alexander N. Plotnikov & Martin J. Walsh & Ming-Ming Zhou, 2010. "Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b," Nature, Nature, vol. 466(7303), pages 258-262, July.
    3. Ghislaine Scelo & Mark P. Purdue & Kevin M. Brown & Mattias Johansson & Zhaoming Wang & Jeanette E. Eckel-Passow & Yuanqing Ye & Jonathan N. Hofmann & Jiyeon Choi & Matthieu Foll & Valerie Gaborieau &, 2017. "Genome-wide association study identifies multiple risk loci for renal cell carcinoma," Nature Communications, Nature, vol. 8(1), pages 1-9, August.
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