Integrin αvβ3 as a Non-Genomic Estrogen Receptor in Breast Cancer for Signaling Pathways and Crosstalk

Abstract

Highlights: What are the main findings? Integrin αvβ3 functions as a crucial non-genomic receptor for estrogen, initiating rapid activation of FAK, ERK1/2, and PI3K signaling pathways. This non-genomic estrogen signaling is shown to critically modulate integrin αvβ3 activity, subsequently driving cancer proliferation, migration, and metastasis What is the implication of the main finding? Crosstalk among estrogen, integrin αvβ3, and GPER generates diverse cellular effects relevant to breast cancer biology. Targeting the Integrin αvβ3 non-genomic axis is proposed as a therapeutic strategy to overcome resistance observed in cancers. Integrin αvβ3, a key member of the integrin family, plays a crucial role in cell localization, mobilization, and signal transduction through collaborating with extracellular proteins. Its unique expression and activation in tumor cells and rapidly dividing endothelial cells suggest its potential role in cancer cell growth and metastasis, making it a promising therapeutic target. In genomic pathways, estrogen binds to its receptors to form transcription complexes that bind to the promoters of steroid hormone-receptive genes. Conversely, G protein-coupled estrogen receptor 1 (GPER) and integrin αvβ3 have been shown to play oles in non-genomic actions that contribute to estrogen-induced cancer growth. The molecular mechanisms of these non-genomic functions involve signal transduction via focal activated kinase (FAK), mitogen-activated protein kinase (ERK1/2), and phosphatidylinositol 3-kinase (PI3K), as well as the differential expression of multiple genes associated with various cellular processes. As a hormone receptor, integrin αvβ3, collaborating with ER-α and GPER, exhibits a wide range of cellular effects relevant to cancer biology.