Estrogen signaling and unfolded protein response in breast cancer

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.