Figure 2.

Proposed model of glyceollin-induced reversion of EMT in letrozole-resistant breast cancer cells. As epithelial breast cancer cells that overexpress aromatase are exposed to prolonged AI therapy (i.e., letrozole) they acquire AI resistance, estrogen independence and undergo morphological changes that are associated with EMT. Once resistance occurs, the levels of HIF-1 are increased, which then controls the expression of ZEB1. ZEB1 expression is induced, which in turn suppresses E-cadherin and induces EMT. However, when letrozole-resistant cells are exposed to glyceollin they undergo morphological changes that are associated with an epithelial-like phenotype, accompanied by a decrease in HIF-1 expression levels. This then causes a decrease in ZEB1 expression, allowing the de-suppression of E-cadherin and the inhibition of EMT. EMT, epithelial to mesenchymal transition; AI, aromatase inhibitor; HIF-1, hypoxia-inducible factor-1; ZEB1, zinc finger E-box-binding homeobox 1.