The SWI/SNF chromatin remodeling factor DPF3 regulates metastasis of ccRCC by modulating TGF-β signaling
Sperling, Silke R.
KAUST DepartmentComputational Bioscience Research Center, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia
Computational Bioscience Research Center (CBRC)
Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division
Computer Science Program
Permanent link to this recordhttp://hdl.handle.net/10754/680209
MetadataShow full item record
AbstractDPF3, 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.
CitationCui, H., Yi, H., Bao, H., Tan, Y., Tian, C., Shi, X., Gan, D., Zhang, B., Liang, W., Chen, R., Zhu, Q., Fang, L., Gao, X., Huang, H., Tian, R., Sperling, S. R., Hu, Y., & Chen, W. (2022). The SWI/SNF chromatin remodeling factor DPF3 regulates metastasis of ccRCC by modulating TGF-β signaling. Nature Communications, 13(1). https://doi.org/10.1038/s41467-022-32472-0
SponsorsThis 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.
PublisherSpringer Science and Business Media LLC
Except where otherwise noted, this item's license is described as Archived with thanks to Nature Communications under a Creative Commons license, details at: https://creativecommons.org/licenses/by/4.0