PMID- 30532986 OWN - NLM STAT- MEDLINE DCOM- 20191118 LR - 20191118 IS - 1208-6002 (Electronic) IS - 0829-8211 (Linking) VI - 97 IP - 4 DP - 2019 Aug TI - Steroid receptor coactivator-1 regulates glioma angiogenesis through polyomavirus enhancer activator 3 signaling. PG - 488-496 LID - 10.1139/bcb-2018-0114 [doi] AB - 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 report that SRC-1 is upregulated in the vessels of human glioma and exerts important regulatory functions. Specifically, SRC-1 expression significantly enhanced basic fibroblast growth factor (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 vascular endothelial growth factor (VEGF) and matrix metallopeptidase (MMP)-9 in glioma cells. These SRC-1-mediated effects were dependent 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 cells, and PEA3 could directly bind with VEGF and MMP-9 promoter under GS4012 treatment in glioma cell. The expression of pro-angiogenic factors induced by SRC-1 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 could be a promising strategy for suppressing tumor angiogenesis. FAU - Zhang, Yi AU - Zhang Y AD - a Department of Neurosurgery, Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, 710004, Shaanxi, People's Republic of China. AD - b Department of Neurosurgery, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, 712000, Shaanxi, People's Republic of China. FAU - Shi, Wei AU - Shi W AD - a Department of Neurosurgery, Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, 710004, Shaanxi, People's Republic of China. LA - eng PT - Journal Article DEP - 20181211 PL - Canada TA - Biochem Cell Biol JT - Biochemistry and cell biology = Biochimie et biologie cellulaire JID - 8606068 RN - 0 (Transcription Factors) RN - 0 (transcription factor PEA3) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) SB - IM MH - Animals MH - Cells, Cultured MH - Glioma/*metabolism MH - Humans MH - Mice MH - Mice, Inbred C57BL MH - Neovascularization, Pathologic/*metabolism MH - Nuclear Receptor Coactivator 1/*metabolism MH - *Signal Transduction MH - Transcription Factors/*metabolism OTO - NOTNLM OT - PEA3 OT - SRC-1 OT - angiogenese tumorale OT - glioma OT - gliome OT - tumor angiogenesis EDAT- 2018/12/12 06:00 MHDA- 2019/11/19 06:00 CRDT- 2018/12/12 06:00 PHST- 2018/12/12 06:00 [pubmed] PHST- 2019/11/19 06:00 [medline] PHST- 2018/12/12 06:00 [entrez] AID - 10.1139/bcb-2018-0114 [doi] PST - ppublish SO - Biochem Cell Biol. 2019 Aug;97(4):488-496. doi: 10.1139/bcb-2018-0114. Epub 2018 Dec 11.