| First Author | Tang YN | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 8230 | PubMed ID | 26354229 |
| Mgi Jnum | J:227015 | Mgi Id | MGI:5699515 |
| Doi | 10.1038/ncomms9230 | Citation | Tang YN, et al. (2015) Epigenetic regulation of Smad2 and Smad3 by profilin-2 promotes lung cancer growth and metastasis. Nat Commun 6:8230 |
| abstractText | Altered transforming growth factor-beta (TGF-beta) 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 unfavourable 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-beta1-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. |
