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; Wei Chen

doi:10.1038/s41467-022-32472-0

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, Wei Chen

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11 Scopus citations

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.

Original language	English (US)
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-32472-0
State	Published - Aug 9 2022

Bibliographical note

KAUST Repository Item: Exported on 2022-09-14
Acknowledgements: This work was supported by the National Natural Science Foundation of China (Grant No. 31900462), Shenzhen Science and Technology Program (Grant No. KQTD20180411143432337), and Shenzhen Key Laboratory of Gene Regulation and Systems Biology (Grant No. ZDSYS20200811144002008). The authors acknowledge the SUSTech Core Research Facilities for technical support and the Center for Computational Science and Engineering of SUSTech for the support of computational resources.

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
General Chemistry
General Physics and Astronomy

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10.1038/s41467-022-32472-0

https://repository.kaust.edu.sa/bitstream/10754/680209/1/s41467-022-32472-0.pdf

Cite this

@article{77f52ffe4e104f96a9cb569770b072ee,

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

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.",

author = "Huanhuan Cui and Hongyang Yi and Hongyu Bao and Ying Tan and Chi Tian and Xinyao Shi and Diwen Gan and Bin Zhang and Weizheng Liang and Rui Chen and Qionghua Zhu and Liang Fang and Xin Gao and Hongda Huang and Ruijun Tian and Sperling, {Silke R.} and Yuhui Hu and Wei Chen",

note = "KAUST Repository Item: Exported on 2022-09-14 Acknowledgements: This work was supported by the National Natural Science Foundation of China (Grant No. 31900462), Shenzhen Science and Technology Program (Grant No. KQTD20180411143432337), and Shenzhen Key Laboratory of Gene Regulation and Systems Biology (Grant No. ZDSYS20200811144002008). The authors acknowledge the SUSTech Core Research Facilities for technical support and the Center for Computational Science and Engineering of SUSTech for the support of computational resources.",

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doi = "10.1038/s41467-022-32472-0",

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T1 - The SWI/SNF chromatin remodeling factor DPF3 regulates metastasis of ccRCC by modulating TGF-β signaling

AU - Cui, Huanhuan

AU - Yi, Hongyang

AU - Bao, Hongyu

AU - Tan, Ying

AU - Tian, Chi

AU - Shi, Xinyao

AU - Gan, Diwen

AU - Zhang, Bin

AU - Liang, Weizheng

AU - Chen, Rui

AU - Zhu, Qionghua

AU - Fang, Liang

AU - Gao, Xin

AU - Huang, Hongda

AU - Tian, Ruijun

AU - Sperling, Silke R.

AU - Hu, Yuhui

AU - Chen, Wei

N1 - KAUST Repository Item: Exported on 2022-09-14 Acknowledgements: This work was supported by the National Natural Science Foundation of China (Grant No. 31900462), Shenzhen Science and Technology Program (Grant No. KQTD20180411143432337), and Shenzhen Key Laboratory of Gene Regulation and Systems Biology (Grant No. ZDSYS20200811144002008). The authors acknowledge the SUSTech Core Research Facilities for technical support and the Center for Computational Science and Engineering of SUSTech for the support of computational resources.

PY - 2022/8/9

Y1 - 2022/8/9

N2 - 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.

AB - 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.

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UR - https://www.nature.com/articles/s41467-022-32472-0

U2 - 10.1038/s41467-022-32472-0

DO - 10.1038/s41467-022-32472-0

M3 - Article

C2 - 35945219

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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