Sno/Ski Proto-Oncogene Family

Many types of tumors result from the misregulation of gene expression. Expression of the human proto-oncogenes Sno and Ski have been correlated with poor outcome in estrogen-receptor-positive breast tumors, and gene amplification at the Sno locus is associated with esophageal squamous cell carcinoma. The viral oncogene v-Ski was discovered in the mid-1980s at the Sloan-Kettering Institute as the transforming factor in a retrovirus isolated from chick embryos. Sno (Ski-related novel gene) was identified soon after, although sequence analysis showed that Sno is evolutionarily much older than Ski. Overexpression studies with Ski and Sno in mammalian cells identified them as antagonists of transforming growth factor-β (TGF-β) tumor-suppressive signals suggesting a basis for their oncogenicity. Loss-of-function studies in several organisms suggested that a normal role for Sno during development might be to facilitate TGF-β signaling. Current work describes regulators of Sno and Ski, while other ongoing analyses suggest that Sno may have functions outside TGF-β signaling via interactions with p53 and the Wnt pathway.