Steroid receptor coactivator-1 regulates glioma angiogenesis through polyomavirus enhancer activator 3 signaling.

Steroid receptor coactivator 1 (SRC-1) is a transcriptional coactivator for steroid receptors and other transcription factors. SRC-1 has been shown to play an important role in the progression of breast cancer and prostate cancer. However, its role in glioma progression remains unknown. Here, in this study, we reported that SRC-1 is upregulated in the vessels of human glioma and exerts important regulatory functions. Specifically, SRC-1 expression significantly enhanced bFGF-mediated angiogenesis in vivo. Downregulating of SRC-1 expression suppressed endothelial cell migration and tube formation in vitro and upregulated the expression of pro-angiogenic factors including VEGF and MMP-9 in glioma cells. These SRC-1-mediated effects were depended on the activation of polyomavirus enhancer activator 3 (PEA3) transcriptional activity. VEGF and VEGF inducer GS4012 induced the direct binding of SRC-1 and PEA3 in glioma cell, and PEA3 could directly bind with VEGF and MMP-9 promoter under GS4012 treatment in glioma cell. The SRC-1 induced pro-angiogenic factors expression was abrogated by sh-PEA3 knockdown. Taken together, these novel outcomes indicated that SRC-1 modulated endothelial cell (EC) function and facilitated a pro-angiogenic microenvironment through PEA3 signaling. Moreover, a combination of targeting SRC-1 and PEA3 signaling in glioma might be a promising strategy by suppressing tumor angiogenesis.