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. Author manuscript; available in PMC: 2013 May 1.
Published in final edited form as: Cancer Res. 2012 Feb 29;72(9):2440–2453. doi: 10.1158/0008-5472.CAN-11-4038

Figure 6. Summary of the proposed model.

Figure 6

EMT is induced by the combination of TGF-β with other micro-environmental factors, and requires the activation of ZEB1 plus other target genes. Microenvironmental factors (Wnt, NF-kb agonists?) up-regulate Twist and Snail genes, which down-regulate GRHL2. This down-regulation alleviates the repression of the ZEB1 promoter, permitting TGF-β (partly, through Twist and Snail themselves) to activate ZEB1 expression. The down-regulation of GRHL2 also enhances Smad-mediated transactivation of TGF-β target genes, which, together with ZEB1, induce EMT and anoikis-resistance.