title: IRX2-mediated upregulation of MMP-9 and VEGF in a PI3K/AKT-dependent manner.
abstract: Osteosarcoma (OS) is the most frequent type of primitive malignant bone tumor with a poor prognosis due to distant metastasis. Our previous studies have demonstrated that IRX2 is overexpressed and is important in cell proliferation and invasion. However, the molecular mechanisms underlying the IRX2‑dependent regulation of OS progression remains to be elucidated. In the present study, the effects of IRX2 on the upregulation of MMP2 and VEGF in OS were determined by western blotting, and the underlying molecular mechanisms were elucidated. These findings provided data suggesting that IRX2 modulates the expression levels of MMP2 and VEGF in an AKT‑dependent manner. The overexpression of IRX2 promoted the activation of PI3K/Akt and increased the proliferation and invasiveness of the OS cell lines as shown by CCK8 and invasion assays. Notably, interruption of the AKT pathway by treatment with LY294002, a specific PI3K inhibitor, attenuated IRX2‑induced cell proliferation and invasive ability, and the upregulation of MMP2 and VEGF. The results of the present study suggested that inhibition of the IRX2‑mediated AKT signaling pathway may be a suitable therapeutic target for the treatment of OS.
authors.affiliation: Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Tielong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, Ningbo Development Zone Center Hospital, Ningbo, Zhejiang 315800, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Orthopedics, First People's Hospital of Hefei, Hefei, Anhui 230061, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chu
authors.affiliation: Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Orthopedics, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Teng
authors.affiliation: Department of Orthopedics, The Workers Hospital of Suqian City, Suqian, Jiangsu 223800, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Jianru
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Orthopedics, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004790:Enzyme Induction; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; C501595:IRX2 protein, human; D014157:Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9