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Minireview: steroid receptor coactivator-3: a multifarious coregulator in mammary gland metastasis

John P Lydon1, Bert W O'Malley

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.

Endocrinology
|November 5, 2010
PubMed

Insights

Steroid receptor coactivator-3 (SRC-3) drives breast cancer invasion and metastasis. This oncogenic coregulator promotes cell motility and extracellular matrix degradation, highlighting its role as a prometastatic factor.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Steroid receptor coactivator-3 (SRC-3) is a member of the SRC/p160 family, acting as a crucial coregulator in various signaling pathways.
  • While SRC-3's role in mammary gland tumor proliferation is known, its function in tumor cell motility and invasion is a recent discovery.
  • SRC-3's pleiotropic nature allows it to influence numerous signaling networks vital for both normal physiology and disease states.

Purpose of the Study:

  • To elucidate the role of SRC-3 in tumor cell motility and invasion within the context of breast cancer.
  • To investigate the mechanisms by which SRC-3 contributes to the early stages of the invasion-metastasis cascade.
  • To explore the potential of SRC-3 as a therapeutic target for breast cancer intervention.

Main Methods:

  • Analysis of SRC-3's nuclear functions in epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) degradation.
  • Investigation of a truncated SRC-3 isoform (SRC-3Δ4) at the plasma membrane as a signaling adaptor.
  • Examination of the epidermal growth factor (EGF) signaling pathway involving focal adhesion kinase (FAK) and c-Src.

Main Results:

  • Nuclear SRC-3 is essential for executing EMT, conferring motility and invasive properties to cancer cells.
  • SRC-3 facilitates the proteolytic breakdown of the ECM by matrix-metalloproteinases, aiding tumor cell invasion.
  • A truncated SRC-3 isoform (SRC-3Δ4) acts as a signaling adaptor in the EGF-induced FAK-c-Src pathway, crucial for cell migration and invasion.

Conclusions:

  • SRC-3 functions as both a proto-oncogene and a prometastatic factor in the early invasion-metastasis cascade of breast cancer.
  • Understanding SRC-3's multifaceted roles provides critical mechanistic insights into mammary tumor progression.
  • These findings offer new avenues for developing diagnostic and therapeutic strategies for breast cancer.

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