Skip to main content
. 2018 Jul 6;9(52):29906–29920. doi: 10.18632/oncotarget.25692

Figure 1. The Notch-EMT-STEM decision-making circuit.

Figure 1

(A) The Notch circuit receives external ligands (Delta/Jagged) as inputs that bind to Notch on the surface. This results in the cleavage of Notch which generates NICD. NICD translocates to the nucleus where it transcriptionally activates Notch and Jagged while inhibiting Delta. (B) The EMT module contains two micro-RNA families (miR-34, miR-200) and two transcription factor families (SNAIL, ZEB) which mutually repress each other. External signals such as Wnt or TGF-beta activate SNAIL and promote EMT. (C) In the STEM module, LIN-28 and let-7 mutually repress each other, while both can self-activate. Additionally, external NF-κB signaling activates both. Solid lines stand for transcriptional/translational interactions (let-7 auto-regulates its maturation), while dotted lines represent post-translational inhibition. The connections between the modules are highlighted in red: NICD transcriptionally activates SNAIL; miR-34 post-translationally inhibits Notch and Delta, while miR-200 inhibits Jagged; miR-200 and let-7 post-translationally inhibit LIN-28 and ZEB respectively.