Hepatocyte growth factor activator (HGFA) (HGFA)

Hepatocyte growth factor activator (HGFA) is a serine protease that plays a pivotal role in the HGF/c-MET signaling axis by converting the inactive single-chain precursor, pro-HGF, into its biologically active heterodimeric form [1, 9]. This proteolytic activation is a rate-limiting step in the activation of the c-MET receptor tyrosine kinase, which regulates essential cellular processes such as proliferation, survival, and motility [3, 5]. HGFA is primarily secreted by the liver as a zymogen (pro-HGFA) and is activated at sites of tissue injury or tumor growth by proteases like thrombin [6, 9]. In various malignancies, HGFA is overexpressed or dysregulated, leading to constitutive c-MET phosphorylation that promotes tumor invasion, metastasis, and resistance to other targeted therapies [4, 12]. Consequently, HGFA is considered a promising therapeutic target, with experimental inhibitors such as small molecules, macrocyclic peptides, and monoclonal antibodies being developed to block HGF activation and indirectly inhibit c-MET signaling [1, 3, 8]. However, because HGFA is also involved in physiological tissue repair and wound healing, its inhibition may pose safety challenges related to impaired regeneration [6, 9].

Other names

HGF activatorHGFACSerine protease 13Hepatocyte growth factor activator precursor

Inhibition of the proteolytic conversion of pro-HGF to active HGF, thereby preventing c-MET receptor activation and downstream phosphorylation.