Western blot further showed that CRC cell-derived CM or Exos upregulated VEGFR, Smad2 and Smad3, but had no significant effect on Smad1, Smad4, Smad6 and Smad7 expression (Fig. 1I), indicating that VEGFR and Smad2/3 pathway might be involved in the enhanced HUVECs angiogenesis caused by CRC cell-derived exosomes. The gene discussed is SMAD4; the disease is colorectal carcinoma.