Rapid regulatory actions of sex steroids on cell movement through the actin cytoskeleton

Cell movement is required in relevant physiological processes such as embryonic development, tissue and organ differentiation, inflammation, immune response and wound healing, along with pathological phenomena, such as cancer metastatic spread. Cell motility is tightly controlled by a complex and often redundant array of intracellular signaling pathways largely devoted to the dynamic regulation of the actin cytoskeletal network and of its relationship with the cell membrane and the extracellular matrix. Sex steroids, particularly estrogen and progesterone, are effective regulators of cell migration and tissue organization, and recent evidence indicates that this is in part obtained through the regulation of the cytoskeleton. Intriguingly, many of these regulatory actions related to cell movement are achieved through rapid, non-classical signaling of sex steroid receptors to kinase cascades, independently from nuclear alteration of gene expression or protein synthesis. The identification of the mechanistic basis for these rapid actions on cell cytoskeleton and cell movement has special relevance for the characterization of the effects of sex steroids in physiological conditions, such their role in the control of inflammation, brain or vascular cell remodelling, angiogenesis or wound healing, as well as in the context of pathological conditions such as steroid-sensitive cancer cell invasion and metastasis. This review highlights the physiological and clinical conditions where the regulatory effects on the cytoskeleton and cell movement of sex steroids might have a special importance, as well as the recent advances in the characterization of the mechanisms, providing insights and working hypotheses on possible clinical applications for the modulation of these pathways. (C) 2008 Elsevier Inc. All rights reserved.