Amphiregulin enhances intercellular adhesion molecule-1 expression and promotes tumor metastasis in human osteosarcoma
Journal
Oncotarget
Journal Volume
6
Journal Issue
38
Pages
40880-40895
Date Issued
2015
Author(s)
Abstract
Osteosarcoma is a common, high malignant, and metastatic bone cancer. Amphiregulin (AREG) has been associated with cancer cellular activities. However, the effect of AREG on metastasis activity in human osteosarcoma cells has yet to be determined. We determined that AREG increases the expression of intercellular adhesion molecule-1 (ICAM-1) through PI3K/Akt signaling pathway via its interaction with the epidermal growth factor receptor, thus resulting in the enhanced cell migration of osteosarcoma. Furthermore, AREG stimulation increased the association of NF-κB to ICAM-1 promoter which then up-regulated ICAM-1 expression. Finally, we observed that shRNA silencing of AREG decreased osteosarcoma metastasis in vivo. Our findings revealed a relationship between osteosarcoma metastatic potential and AREG expression and the modulating effect of AREG on ICAM-1 expression.
SDGs
Other Subjects
amphiregulin; epidermal growth factor receptor; immunoglobulin enhancer binding protein; intercellular adhesion molecule 1; phosphatidylinositol 3 kinase; protein kinase B; short hairpin RNA; small interfering RNA; amphiregulin; AREG protein, human; EGFR protein, human; epidermal growth factor derivative; epidermal growth factor receptor; ICAM1 protein, human; immunoglobulin enhancer binding protein; intercellular adhesion molecule 1; messenger RNA; phosphatidylinositol 3 kinase; animal experiment; animal model; animal tissue; Article; cancer cell culture; cell migration; cell proliferation; chromatin immunoprecipitation; controlled study; genetic transfection; human; human cell; in vivo study; lung metastasis; male; mouse; nonhuman; osteosarcoma; osteosarcoma cell; promoter region; protein expression; protein interaction; real time polymerase chain reaction; reporter gene; signal transduction; tumor xenograft; upregulation; Western blotting; animal; apoptosis; bone tumor; cell motion; chemistry; drug screening; enzyme immunoassay; genetics; lung tumor; metabolism; osteosarcoma; pathology; reverse transcription polymerase chain reaction; SCID mouse; secondary; tumor cell culture; Amphiregulin; Animals; Apoptosis; Blotting, Western; Bone Neoplasms; Cell Movement; Cell Proliferation; Chromatin Immunoprecipitation; EGF Family of Proteins; Humans; Immunoenzyme Techniques; Intercellular Adhesion Molecule-1; Lung Neoplasms; Male; Mice; Mice, SCID; NF-kappa B; Osteosarcoma; Phosphatidylinositol 3-Kinases; Real-Time Polymerase Chain Reaction; Receptor, Epidermal Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Signal Transduction; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
Publisher
Impact Journals LLC
Type
journal article