Crosstalk between Estrogen Signaling and Breast Cancer Metabolism

Different breast cancer subtypes have different metabolic phenotypes. ERs modulate the expression of genes important for metabolic regulation. Extranuclear ERs regulate kinase signaling pathways as well as mitochondrial metabolism to modulate cancer cell metabolism. Metabolic rewiring is an inherent property of endocrine resistance, but it is not clear whether it is a driver or consequence of endocrine resistance. Estrogens and estrogen receptors (ERs) regulate metabolism in both normal physiology and in disease. The metabolic characteristics of intrinsic breast cancer subtypes change based on their ER expression. Crosstalk between estrogen signaling elements and several key metabolic regulators alters metabolism in breast cancer cells, and enables tumors to rewire their metabolism to adapt to poor perfusion, transient nutrient deprivation, and increased acidity. This leads to the selection of drug-resistant and metastatic clones. In this review we discuss studies revealing the role of estrogen signaling elements in drug resistance development and metabolic adaptation during breast cancer progression. Estrogens and estrogen receptors (ERs) regulate metabolism in both normal physiology and in disease. The metabolic characteristics of intrinsic breast cancer subtypes change based on their ER expression. Crosstalk between estrogen signaling elements and several key metabolic regulators alters metabolism in breast cancer cells, and enables tumors to rewire their metabolism to adapt to poor perfusion, transient nutrient deprivation, and increased acidity. This leads to the selection of drug-resistant and metastatic clones. In this review we discuss studies revealing the role of estrogen signaling elements in drug resistance development and metabolic adaptation during breast cancer progression.