78 kDa gastrin-binding protein (GBP)

The 78 kDa gastrin-binding protein (GBP) is a high-affinity binding site for the hormone gastrin, primarily identified in the gastric mucosa and various gastrointestinal tissues (Baldwin et al., 1994, J Biol Chem). Molecular characterization has revealed that this protein is identical to the peroxisomal bifunctional enzyme, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (EHHADH) (UniProt Q08426). While its primary metabolic function involves the second and third steps of the peroxisomal fatty acid beta-oxidation pathway, it also localizes to the cell membrane where it may mediate the trophic effects of gastrin (He et al., 2001, Biochem J). The 78 kDa GBP is significantly overexpressed in colorectal, gastric, and pancreatic cancers, where it is thought to promote cell proliferation and tumor growth independently of the classical Cholecystokinin B receptor (CCKBR) (Smith & Watson, 2000, Aliment Pharmacol Ther). As a potential therapeutic target, research has focused on using antisense oligonucleotides or specific antibodies to inhibit its expression or activity in gastrointestinal malignancies (Baldwin, 1995, Progress in Nucleic Acid Research and Molecular Biology). However, targeting this protein poses significant safety concerns due to its essential role in systemic lipid metabolism and peroxisomal function.

Other names

Gastrin-binding proteinEnoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenaseEHHADHL-bifunctional enzymep78Peroxisomal bifunctional enzyme

Antagonism of gastrin binding to the 78 kDa GBP to inhibit gastrin-stimulated cellular proliferation in gastrointestinal tumors.