Hepatocyte growth factor activator (HGFA)

Hepatocyte growth factor activator (HGFA) is a specialized serine protease secreted primarily by the liver as an inactive zymogen that circulates in the blood. Following tissue injury or during tumor progression, it is activated by thrombin or kallikreins, where it then catalyzes the proteolytic cleavage of the inactive single-chain precursor of hepatocyte growth factor (pro-HGF) into its active, bioactive heterodimeric form (UniProt P35944; PubMed 8387494). This activation is a critical rate-limiting step in the HGF/MET signaling pathway, which regulates cell proliferation, motility, and survival (PubMed 25253381). In oncology, HGFA is frequently upregulated or dysregulated, leading to constitutive MET activation that drives tumor growth, epithelial-to-mesenchymal transition (EMT), and metastasis (PubMed 16113098). Therapeutic strategies focus on inhibiting HGFA to block the HGF/MET axis, particularly in cancers that are resistant to direct MET kinase inhibitors or where HGF overproduction is a primary driver of resistance. Because HGFA's physiological role is tied to wound healing and organ regeneration, pharmacological targeting requires careful management to avoid systemic toxicities related to impaired tissue repair (PubMed 20008546).

Other names

HGF activatorHGFACHepatocyte growth factor activator precursorHGF-activating protease

Inhibition of the proteolytic conversion of inactive single-chain pro-hepatocyte growth factor (pro-HGF) into its active heterodimeric form, thereby preventing the activation of the MET receptor tyrosine kinase signaling pathway.