FIGURE 7.

Diagram of the molecular pathway that leads to EMT downstream of TGFβ and HMGA2, as analyzed in this study. TGFβ, via Smads induces expression of HMGA2. HMGA2 then binds to the promoters of Snail and Twist and induces their expression. The Snail gene also receives additional inputs from TGFβ, such as ERK MAPK signaling. The five pro-EMT transcription factors (boxed) positively cross-regulate each other to elicit nuclear reprogramming that leads to EMT. Snail and Twist cross-regulate expression of each other albeit weakly (dotted arrow). Snail regulates expression of Slug, ZEB1, and ZEB2, whereas Twist regulates expression of Slug and ZEB1. The possible cross-regulation between ZEB1, ZEB2, and Slug was not examined in this study.