GREM1 was reported to mediate hyperplasia and the invasiveness of rheumatoid arthritis synoviocytes through activation of ERK and Akt.45 GREM1 activates Akt signalling to promote proliferation, migration and VEGF production in retinal pigmentation epithelial cells.46 In addition, GREM1 activates Smad9 or Slug47,48 to facilitate EMT and cancer cell growth. This evidence concerns the gene SMAD9 and cancer.