The network of pluripotency, epithelial–mesenchymal transition, and prognosis of breast cancer

Figures & data

Figure 1 Schematic representation of the cooperative action of pluripotency transcription factors on promoters of target genes.

Notes: Oct4 and Sox2 often work in synergy to transcribe genes such as Nanog which then cooperate with them on additional targets. c-myc facilitates the process by helping create permissive chromatin modifications. LIN28 neutralizes the inhibitory effect of mRNA let-7 on c-myc. Arrows denote activation and ⊢ denotes inhibition.

Figure 2 The road to EMT.

Notes: EMT core transcription factors such as Snail and Slug, ZEB1 and ZEB2, Twist, and TCF3 cooperate to establish EMT by suppressing E-cadherin and other actions. They are under control of multiple regulators that activate or inhibit them. Examples of these regulatory factors are depicted. Arrows denote activation and ⊢ denotes inhibition. The thick arrow pointing to EMT illustrates that the process is progressive, with several factors acting along the way, as discussed in the text.
Abbreviation: EMT, epithelial–mesenchymal transition.

Figure 3 An overview of the close relationship of the EMT and pluripotency networks.

Notes: Only some regulations are illustrated to preserve clarity. Arrows denote activation and ⊢ symbols inhibition.
Abbreviation: EMT, epithelial–mesenchymal transition.

Figure 4 Regulation of ER by pluripotency and EMT factors.

Notes: Oct4, Sox2, Nanog, and Twist overexpression leads to suppression of ER. In addition, Sox2 has an indirect influence on ER expression and function by suppressing pioneer factor FOXA1. These effects contribute to suppression of ER expression in cancer stem cells where the pluripotency network is in place. ER promotes MET and expression of Oct4, but an established pluripotency network may render Oct4 expression independent of ER expression. Arrows denote activation and ⊢ symbols inhibition.
Abbreviation: MET, mesenchymal–epithelial transition.

Figure 5 A proposed model of the cooperation of pluripotency and EMT/MET processes in metastasis establishment.

Notes: According to this model, a cell undergoing EMT would be able to establish a metastatic focus only if the pluripotency network is in place to endow it with the genetic plasticity required to undergo the reverse process, MET.
Abbreviations: EMT, epithelial–mesenchymal transition; MET, mesenchymal–epithelial transition.