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.