Abstract
Transforming growth factor-beta is a potent inhibitor of epithelial cell proliferation. Proteins involved in TGF-β signaling are bona fide tumor suppressors and many tumor cells acquire the ability to escape TGF-β growth inhibition through the loss of key signaling transducers in the pathway or through the activation of oncogenes. Recent studies indicate that there is a specific connection between the TGF-β signaling pathway and the Ski/SnoN family of oncoproteins. We summarize evidence that Ski and SnoN directly associate with Smad proteins and block the ability of the Smads to activate expression of many if not all TGF-β-responsive genes. This appears to cause abrogation of TGF-β growth inhibition in epithelial cells.
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