pigenetic regulation of Smad2 and Smad3 by profilin-2 promotes lung cancer growth and metastasis
pigenetic regulation of Smad2 and Smad3 by profilin-2 promotes lung cancer growth and metastasis
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DOI：
10.1038/ncomms9230
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发表时间：
2015
影响因子：
16.6
通讯作者：
Jian-Guo Song
中科院分区：
文献类型：
--
作者：
Yun-Neng Tang;Wei-Qiao Ding;Xiao-Jie Guo;Xin-WangYuan;Dong-Mei Wang;Jian-Guo Song
Altered transforming growth factor-b (TGF-b) signalling has been implicated in tumour development and progression. However, the molecular mechanism behind this alteration is poorly understood. Here we show that profilin-2 (Pfn2) increases Smad2 and Smad3 expression via an epigenetic mechanism, and that profilin-2 and Smad expression correlate with an unfavorable prognosis of lung cancer patients. Profilin-2 overexpression promotes, whereas profilin-2 knockdown drastically reduces, lung cancer growth and metastasis. We show that profilin-2 suppresses the recruitment of HDAC1 to Smad2 and Smad3 promoters by preventing nuclear translocation of HDAC1 through protein–protein interaction at the C terminus of both proteins, leading to the transcriptional activation of Smad2 and Smad3. Increased Smad2 and Smad3 expression enhances TGF-b1-induced EMT and production of the angiogenic factors VEGF and CTGF. These findings reveal a new regulatory mechanism of TGF-beta1/Smad signalling, and suggest a potential molecular target for the development of anticancer drugs.
