Oncogenic MET-mutants are responsible for papillary renal carcinomas and head-and-neck carcinoma, but these are not common in many types of malignant tumors. In contrast, HGF plays common roles in cancer metastasis, independent of the presence or absence of MET mutations. Tumor cell scattering in the primary tumors is the first step for metastasis. In tumor tissues, stroma-secreted HGF is required for cancer cells to infiltrate neighboring tissues, such as vascular beds, across the basement membrane. The paracrine loop between HGF-producing stroma and MET-expressing tumor cells acts as a local switch for the invasive phenotypes. In addition to adjacent invasion, the HGF–MET axis is important for distant metastasis, through extravasation, anti-anoikis and homing. HGF promotes cancer metastasis via inducing vascular bed formation and enhancing chemokine-induced homing. HGF also protects cancer cells from anoikis or immunological challenge. These sequential events lead to successful metastasis.
Cecchi F, Rabe D C, Bottaro D P. Targeting the HGF/Met signaling pathway in cancer therapy[J]. Expert opinion on therapeutic targets, 2012, 16(6): 553-572.
Mizuno S, Nakamura T. HGF–Met cascade, a key target for inhibiting cancer metastasis: The impact of NK4 discovery on cancer biology and therapeutics[J]. International journal of molecular sciences, 2013, 14(1): 888-919.