CUTL1: a key mediator of TGFbeta-induced tumor invasion.

The TGFbeta pathway plays a dual role in human carcinogenesis. On one hand, TGFbeta is well known for its ability to inhibit epithelial cell proliferation and promote apoptosis. However, many advanced cancers acquire resistance to the growth-inhibitory effects of TGFbeta and respond to it instead with promotion of proliferation, invasion and tumor progression. The homeobox transcription factor CUTL1, also known as CCAAT displacement protein, CDP or Cux-1, is involved in the control of normal embryonic development and differentiation. Recently, we found that CUTL1 is a transcriptional target of TGFbeta and is an important mediator of the TGFbeta-induced cell migration and invasion. In addition, CUTL1 is highly expressed in various epithelial cancers and seems to negatively correlate with tumor differentiation and patient survival. Therefore we postulate that CUTL1 might be a key mediator of the tumor-promoting effects of TGFbeta in advanced cancers.