Mechanism of epigenetic regulation of lung cancer growth and metastasis

Mechanism of epigenetic regulation of lung cancer growth and metastasis

Altered transforming growth factor-β (TGF-β) signalling has been implicated in tumor development and progression. However, the molecular mechanism behind this alteration is poorly understood.

Authors in the journal Nature Communications 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.

Authors 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-β1-induced EMT and production of the angiogenic factors VEGF and CTGF.

These findings reveal a new regulatory mechanism of TGF-β1/Smad signalling, and suggest a potential molecular target for the development of anticancer drugs.

http://www.nature.com/ncomms/2015/150910/ncomms9230/full/ncomms9230.html
Edited

Rating

Unrated
Rating: