Co-culture studies of liver cancer cells expressing high levels of TIMP-1 with fibroblasts extracted from normal liver demonstrated accelerated proliferation, migration and invasion of liver fibroblasts through activation of stromal derived factor-1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4)/PI3K/AKT signaling pathways, indicating that TIMP-1 promotes hepatocellular carcinoma through activation of cancer associated fibroblasts [178]. This evidence concerns the gene TIMP1 and hepatocellular carcinoma.