Figure 3

Schematic representation of ERβ-mediated antitumor pathways. After receptor dimerization, ERβ enhances expression of E-cadherin, a protein that maintains epithelial integrity by blocking EMT. In addition, ERβ upregulates transcription of PHD2 and FOXO3a. In turn, PHD2 marks HIF-1α for destruction, resulting in the suppression of the oncogenic genes LOX, VEGF and TWIST and therefore preventing epithelial dedifferentiation, invasion and metastasis. ERβ through FOX3α, induce apoptosis by upregulating the proapoptotic factor PUMA and cell cycle regulators p21 and p27. ERβ antitumor effects are inhibited by oxidative stress and paracrine signals including TGF-β signaling and hypoxia.