Sex-steroid rapid action and its role in invasiveness and metastasis of breast cancer

Abstract

Sex steroids, particularly estrogen and progesterone, promote normal breast tissue growth and differentiation. Prolonged exposure of estrogen and/or progesterone is well-documented to be the risk factor for breast cancer carcinogenesis, while the effects of sex steroids on breast cancer metastasis are controversial. Recent years emerging evidence indicate that sex steroids regulate the breast cancer metastatic processes via nongenomic and genomic mechanisms. Through nongenomic activation of actin-binding proteins, both estrogen and progesterone rapidly provoke actin cytoskeleton reorganization in breast cancer cells, leading to the formation of membrane specialized structures that facilitate breast cancer cell migration and invasion. Meanwhile, liganded-membrane steroid receptors interact and transactivate receptor tyrosine kinases (including epidermal growth factor receptor and insulin-like growth factor receptor), resulting in growth factor-like effects that transform cancer cell into an invasive phenotype. Moreover, sex steroids regulate the expression patterns of metastasis-associated molecules, such as cell adhesion molecule E-cadherin, matrix metalloproteinases, growth factors, chemokines and their receptors, leading to epithelial-to-mesenchymal-like transition and promoting breast cancer cells escape from primary site and migrate toward target tissues and organs. On the opposite, there is also evidence that sex steroids and their receptors protect against breast cancer cell invasiveness through distinct mechanisms. In this chapter, we present a brief overview of the molecular mechanisms of sex steroids on breast cancer metastasis and the understanding in this topic will be of most importance clinical therapies on breast cancer metastasis.