Gastrokine 1, previously known as AMP-18, CA11, FOVEOLIN and TFIZ, was formally named “GKN1” by the HUGO gene Nomenclature Committee for its gastric-specific expression and its highly conserved presence in the gastric mucosa of many mammalian species. Gastrokine 1 is a novel protein that was firstly cloned by a Japanese group in 2000. GKN1 belongs to a family of genes encoding stomach-specific secreted proteins consisting of 3 known members: gastrokine 1 (GKN1), gastrokine 2 (GKN2) and gastrokine 3 (GKN3). GKN1 gene of about 6 kb was reported to be located at 2p13 and contains 6 exons. The GKN1 gene encodes a small protein of 185 amino acids containing a N-terminal signal peptide. It is a secreted protein with a molecular weight of approximately 18 kDa. GKN1 protein contains a BRICHOS domain, which is associated with dementia, respiratory distress and cancer. Molecular studies on the BRICHOS domain function have suggested that it has a range of possible roles, including intracellular trafficking, propeptide processing, chaperone function and secretion. However, the biological activities of the BRICHOS domain in GKN1 have not been elucidated. Gastrokine 1 has been detected recently in normal gastric mucosa, but not in other regions of the gastrointestinal tract. Immunoelectron microscopy indicated that the GKN1 protein is localized within the granules just under the apical plasma membrane. These expression patterns of GKN1 indicate that it may play a distinctive role in the stomach. Functionally, GKN1 promotes the maturation of gastric mucosa, and maintains the integrity of gastric mucosal epithelium through mitogenic and mutagenic abilities. GKN1 may also protect the intestinal mucosal barrier by acting on specific tight junction proteins and stabilizing perijunctional actin. If the protein is downregulated, the repair process may be impaired. Recently, a number of studies have found that deficiency of GKN1 can result in instability of the gastric epithelium. Clinically, GKN1 is downregulated in Helicobacter pylori-infected gastric epithelial cells, and this loss of GKN1 expression is detected in gastric cancer and precancerous lesion, such as intestinal metaplasia. Invasive factor such as H. pylori contribute to the downregulation of GKN1, whilst inducing ulceration and cancer. Moreover, GKN1 plays an important role in epithelial-mesenchymal transition and migration of gastric cancer cells by regulating reactive oxygen species (ROS) and the P13K/Akt pathway. Recently, it has been suggested that GKN1 induces senescence through activating p16/Rb pathway in gastric cancer cells. Thus, GKN1 may play a key role in the progression of gastric cancer, and may be a potential biomarker for the early detection of gastric cancer.
Shopping cart $0
Search