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. 2007 Jul 23;98(10):1512–1520. doi: 10.1111/j.1349-7006.2007.00550.x

Figure 4.

Figure 4

The transcriptional program of transforming growth factor (TGF)‐β that elicits epithelial–mesenchymal transition (EMT). TGF‐β activates Smad complexes that act together with other transcription factors (TF) and induce expression of several other transcription factors. Gene targets are shown as circles. Black circles represent gene repression, while white circles represent gene induction. Id2 and Id3 inhibit E‐box‐binding proteins such as E12/E47 and possibly Twist (?). HMGA2 induces further expression of Twist, Slug or Snail. All these transcriptional repressors down‐regulate E‐cadherin expression. ZEB‐1 and LEF‐1 are transcriptionally induced and together with ZEB‐2 participate in transcriptional complexes with Smads, and repress the E‐cadherin gene. Jagged‐1 (JAG‐1) activates the Notch pathway (dotted arrow), which possibly induces expression of Snail (?). CUTL induces expression of Wnt‐5, which activates the β‐catenin pathway (dotted arrow), thus mobilizing transcription factor LEF‐1. Finally, Smad complexes induce expression of α‐smooth muscle actin (α‐SMA), fibronectin (FN), PAI‐1, vimentin and N‐cadherin, which contribute to the establishment of the motile, mesenchymal cell.