Fig. 8.

Nogo-B receptor (NgBR) is required for epidermal growth factor (EGF)-acquired resistance to tamoxifen in patients with estrogen receptor alpha (ERα)-positive breast cancer. EGF binds to EGF receptor (EGFR) and recruits SOS1, an activator for Ras, to the plasma membrane. NgBR promotes the translocation of Ras to the plasma membrane and enhances EGF signaling, such as phosphorylation of Akt and extracellular signal-related kinase (ERK). Phosphorylated Akt further induces the phosphorylation of MDM2, which promotes p53 ubiquitination leading to its degradation and attenuates p53-mediated apoptosis. Phosphorylation of Akt and ERK also induce the phosphorylation of ERα, which induces the expression of survivin, an apoptosis inhibitor