SOCS4 and gastric cancer: SOCS4 expression was also found to be significantly lower in gastric cancer compared to noncancerous gastric tissue, along with hypermethylation of CpG sites in the promoter region of the SOCS4 gene leading to its silencing [260]. In vivo studies using mouse models also suggest a tumor suppressor role for SOCS4 in epithelial cells via RUNX1-mediated repression of the SOCS4 promoter, leading to decreased SOCS4 levels and increased STAT3 activity, promoting tumor development [261].