title: Steroid receptor co-activator-3 promotes osteosarcoma progression through up-regulation of FoxM1.
abstract: Increasing evidence suggests that the three homologous members of steroid receptor co-activator (SRC) family (SRC-1, SRC-2, and SRC-3) play key roles in enhancing cell proliferation in various human cancers, such as breast, prostate, and hepatocellular carcinoma. However, the function of SRC-3 in osteosarcoma remains largely unexplored. In the current study, we found that SRC-3, but not SRC-1 and SRC-2, was dramatically up-regulated in human osteosarcoma tissues, compared with adjacent normal tissues. To explore the functions of SRC-3 in osteosarcoma, in vitro studies were performed in MG63 and U2OS cells. SRC-3 overexpression promoted osteosarcoma cell proliferation, whereas knockdown of SRC-3 inhibits its proliferation. In support of these findings, we further demonstrated that SRC-3 up-regulated FoxM1 expression through co-activation of C/EBPγ. Together our results show that SRC-3 drives osteosarcoma progression and imply it as a therapeutic target to abrogate osteosarcoma.
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng St, Nangang, Harbin, Heilongjiang, 150001, China, Geng_Shuo@yeah.net.
authors.forename: Shuo
authors.initials: S
authors.lastname: Geng
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.forename: Hepeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Baoxin
authors.initials: B
authors.lastname: Li
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Bi
authors.forename: Chenglin
authors.initials: C
authors.lastname: Yang
mesh_terms: D001665:Binding Sites; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D056921:Nuclear Receptor Coactivator 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D011401:Promoter Regions, Genetic; D015854:Up-Regulation
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C405462:CCAAT-enhancer-binding protein-gamma; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3