Abrogation of transforming growth factor-beta signaling in pancreatic cancer.

Transforming growth factor-beta (TGFbeta) functions as a growth inhibitor for many cell types by inhibiting cell cycle progression. Loss of TGFbeta responsiveness can lead to deregulated cell proliferation and ultimately tumor progression. For example, the TGFbeta signaling pathway is a frequent target for inactivation in pancreatic cancer. Functional connection between the potent growth inhibitory activity of TGFbeta and the tumor suppressor activity of Smads has been well documented. Smads directly modulate transcription of the genes involved in cell cycle progression in response to TGFbeta, and that abrogation of this regulation leads to tumor progression. In this review, we summarize recent research progress on TGFbeta signaling and pancreatic cancer.