Minireview: Steroid Receptor Coactivator-3: A Multifarious Coregulator in Mammary Gland Metastasis

作者: John P. Lydon , Bert W. O'Malley

DOI: 10.1210/EN.2010-1012

关键词:

摘要: A member of the steroid receptor coactivator (SRC)/p160 family, SRC-3 acts as a coregulator for nuclear (NR) and non-NR transcription factors. Such pleiotropy enables to influence myriad signaling networks that are essential normal physiology pathophysiology. Although SRC-3’s proliferative role in primary tumor formation mammary gland is well established, this oncogenic cell motility invasion has only recently been elucidated. In nucleus, required execution epithelial–mesenchymal transition, programming step which endows an immotile cancer with motile invasive characteristics. Nuclear also proteolytic breakdown extracellular matrix by matrix-metalloproteinases, process into surrounding stroma. At plasma membrane, however, truncated isoform (SRC-3Δ4) serves adaptor epidermal growth factor→focal adhesion kinase→c-Src signal transduction pathway, cascade central factor–induced migration invasion. Together, these studies underscore pivotal not proto-oncogene but prometastatic factor during early steps invasion-metastasis cascade. Beyond furnishing critical mechanistic insights involvement progression, findings provide opportunities develop new approaches breast diagnosis intervention.

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