Oncogenic PAK4 regulates Smad2/3 axis involving gastric tumorigenesis

摘要: The alteration of p21-activated kinase 4 (PAK4) and transforming growth factor-beta (TGF-β) signaling effector Smad2/3 was detected in several types tumors, which acts as oncogenic factor tumor suppressor, but the relationship between these events has not been explored. Here, we demonstrate that PAK4 interacts with modulates phosphorylation via both kinase-dependent kinase-independent mechanisms, attenuate axis transactivation TGF-β-mediated inhibition gastric cancer cells. First, interaction Smad2/3, is independent activity, blocks TGF-β1-induced Smad2 Ser465/467 or Smad3 Ser423/425 consequent activation. In addition, phosphorylates on Ser465, leading to degradation through ubiquitin–proteasome-dependent pathway under hepatocyte (HGF) stimulation. Interestingly, expression correlates negatively phospho-Ser465/467 positively phospho-Ser465 tissues. Furthermore, expressions HGF, phospho-Ser474 are markedly increased tissues, decreased Our results document an role repression involved tumorigenesis, suggest a potential therapeutic target for cancer.