TGF-b signaling plays very important roles in the progression of cancers. However, the mechanism that the alteration and the effect of TGF-b signaling utilized remains to be better understood.   

Researchers in the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences have found that a molecule called profilin-2 strongly promotes the lung cancer growth and metastasis. Mechanistic study uncovered a new way that upregulates the TGF-b/Smad2/3 signaling pathway and thus is implicated in the lung cancer progression (see illustration below). 

Profilin-2 is a classic molecule that is involved in the regulation of polymerization and depolymerization of filamentous actin. Profilin-2 is increased in most human lung cancer tissues and is highly positively correlated with the Smad2 and Smad3 (Smad2/3), but negatively correlated with the 5-year survival rates of lung cancer patients.  

Prof. SONG Jianguo and his colleagues discovered that the increase in profilin-2 significantly elevated the Smad2/3 transcriptional expression, leading to the enhancement of TGF-b signaling and relevant biological events and thus promoting the growth and distinct organ metastasis of lung cancer cells. 

Histone deacetylase is an important epigenetic regulator involved in various patho-physiological processes. Further investigations showed that the nuclear translocation of HDAC1 inhibits the transcriptional activation of Smad2/3. Interestingly, SONG and his colleagues identified that profilin-2 promotes the Smad2/3 transcription by direct interacts with HDAC1 and sequesters it in the cytosol. Besides, they also observed a relevant functional relationship between profilin-2 and profilin-1 in the control of lung cancer growth and metastasis.  

Their studies provide an understanding on the role of profilin-2 and the underlying mechanism implicated in the progression of lung cancers. This study is of importance for strategic considerations of the mechanism-based research and development of drugs for the treatment of lung cancers.

The research is accomplished under the support of grants from the Ministry of Science and Technology of China and the National Natural Science Foundation of China. 

Schemastic illustration: The role and underlying mechanism of profilin in lung cancer progression. (Image by Prof. SONG Jianguo`s group)