Estrogen signaling and unfolded protein response in breast cancer. Issue 163 (October 2016) - Rajapaksa, Gayani
Highlights: UPR correlates with therapy resistance in breast cancer. Estrogen activates all three arms of the UPR in ERα-positive tumors. ERα mediates a cytoprotective UPR that assists tumors to resist therapy. Regulation of the UPR is a new role for ERβ in breast cancer. Therapies with ER ligands that decrease protective UPR signaling are being tested. Abstract: Activation of the unfolded protein response (UPR) confers resistance to anti-estrogens and chemotherapeutics in estrogen receptor α (ERα)-positive and triple-negative breast cancers. Among the regulators of the UPR in breast cancer is estrogen signaling. Estrogen regulates major components of the UPR and ER expression is associated with the sensitivity of tumor cells to UPR-regulated apoptosis. Recent studies have confirmed the crosstalk between the ERs and UPR and suggest novel therapeutic strategies that combine targeting of both signaling pathways. These remedies may be more effective in repressing oncogenic adaptive mechanisms and benefit patients with resistant disease.