HGF and colorectal carcinoma: COX-2/PGE(2) pathway as an important mediator of HGF/Met signaling is closely associated with the survival, proliferation and invasion of CRC cells.135 HGF/Met signaling is an important regulator of the COX-2/PGE 2 pathway in CRC cells, stimulating PGE 2 synthesis via COX-2 upregulation and inhibiting PGE 2 degradation via Ras-MAPK/ERK while PI3K/AKT signaling mediate HGF-driven 15-PGDH downregulation.136 In fact, IL-6/IL-6R, HGF/c-Met, STAT3, VEGF cytokinetic pathway is a major mechanism of the pro-oncogenic effect induced by hepatic RFA.137