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Steroid Receptor Coactivator-3/AIB1 Promotes Cell Migration and Invasiveness through Focal Adhesion Turnover and Matrix Metalloproteinase Expression

¹ Department of Molecular and Cellular Biology, ² Department of Pathology, ³ Department of Medicine, ⁴ Program of Development, and ⁵ Baylor Prostate Cancer Specialized Programs of Research Excellence, Baylor College of Medicine, Houston, Texas

Requests for reprints: Ming-Jer Tsai, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030. Phone: 713-798-6253; Fax: 713-798-8227; E-mail: mtsai{at}bcm.tmc.edu.

Key Words: SRC-3/AIB1 • prostate cancer • migration • invasion • MMP

Steroid receptor coactivator-3 (SRC-3)/AIB1 is a member of the p160 nuclear receptor coactivator family involved in development and cell cycle progression. We previously showed that SRC-3/AIB1 is required for prostate cancer cell proliferation and survival. Here, we reported that the elevated SRC-3/AIB1 expression is significantly correlated with human prostate cancer seminal vesicle invasion and lymph node metastasis. Furthermore, SRC-3/AIB1 is associated with increased prostate cancer cell migration and invasion. SRC-3/AIB1 is required for focal adhesion turnover and focal adhesion kinase activation. In addition, SRC-3/AIB1 directly regulates transcription of matrix metalloproteinase (MMP)-2 and MMP-13 through its coactivation of AP-1 and PEA3. Taken together, these data suggest that SRC-3/AIB1 plays an essential role in prostate cancer cell invasion and metastasis. [Cancer Res 2008;68(13):5460–8]