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

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, Silke R. Sperling, Yuhui Hu and Wei Chen ()
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Huanhuan Cui: Southern University of Science and Technology
Hongyang Yi: Southern University of Science and Technology
Hongyu Bao: 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
Liang Fang: Southern University of Science and Technology
Xin Gao: King Abdullah University of Science and Technology (KAUST)
Hongda Huang: 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
Wei Chen: Southern University of Science and Technology

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32472-0

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