Decreased expression of the type III TGF-β receptor enhances metastasis and invasion in hepatocellullar carcinoma progression

The transforming growth factor beta (TGF-beta) superfamily of cytokines is multifunctional and involved in the regulation of cell growth and differentiation. TGF-beta can induce an epithelial-mesenchymal transition (EMT) of both epithelial and endothelial cells. This has consequences for cancer progression in regards to both migration and invasion abilities. The type III TGF-beta receptor (T beta RIII) is a ubiquitously expressed TGF-beta co-receptor which regulates TGF-beta signaling and the progression of various types of cancer. Previous studies have shown that T beta RIII exhibits abnormal expression and plays an essential role in regulating cancer invasion and metastasis, while little is known in regards to its role in hepatocellular carcinoma (HCC) progression. In the present study, we designed the present research to study the role of T beta RIII in the invasion and metastasis of HCC and the possible mechanisms involved. The results demonstrated decreased expression of T beta RIII in HCC patient tissues and human HCC cell lines. TGF-beta 1 stimulation led to the increased migratory ability and reduced expression of T beta RIII in HCC cells. In addition, knockdown of T beta RIII by small interfering RNA (siRNA) promoted the migration and invasion of HCC cells and induced activation of the Smad2 and Akt pathways. All the results suggest that T beta RIII is a novel suppressor of HCC progression.