TY - JOUR
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.
UR - http://hdl.handle.net/10754/680209
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 -
