GSE175845
The SWI/SNF chromatin remodeling factor DPF3 regulates metastasis of ccRCC by modulating TGF-ß signaling [RNA-seq]
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 remained unknown.  In this study, we demonstrated that DPF3a, the short isoform of DPF3, could promote kidney cancer cell migration both in vitro and in vivo, consistent with the clinical observation that DPF3a was significantly upregulated in ccRCC patients with metastasis. Mechanistically, DPF3a specifically interacted with  SNIP1, via which it formed a complex with SMAD4 and p300 histone acetyltransferase (HAT), the major transcriptional regulators of TGF-ß signaling pathway. Moreover, the binding of DPF3a could release the repressive effect of SNIP1 on p300 HAT activity, leading to increased local histone acetylation and activation of cell movement related genes. In summary, our findings uncovered a novel link between chromatin remodeling and tumor metastasis, whose inhibition is a key therapeutic goal for ccRCC treatment. Overall design: RNA-seq in 786-O cells