HIN-1, an inhibitor of cell growth, invasion, and AKT1 activation

Excerpt

High in normal 1 (HIN-1) is a small, secreted protein that was initially identified as a protein the expression of which is lost in the vast majority of breast cancers. The silencing of HIN-1 expression is due to methylation of its promoter, which in addition to breast cancer also occurs in a significant fraction of many other types of solid tumors including prostate cancer, lung cancer, pancreas cancer, and retinoblastoma, suggesting a potential tumor suppressor function. Consistent with this hypothesis, in non-small-cell lung cancer, downregulation of HIN-1 expression was found to be the most significant independent predictor of poor clinical outcome in stage I disease, suggesting loss of HIN-1 expression is a functionally important event. The receptor of HIN-1 is unknown, but ligand-binding studies indicate the presence of high-affinity cell surface HIN-1 binding sites on the same epithelial cells that express HIN-1, suggesting that HIN-1 functions as an autocrine factor. …