Transforming growth factor alpha promotes osteosarcoma metastasis by ICAM-1 and PI3K/Akt signaling pathway
Journal
Biochemical Pharmacology
Journal Volume
89
Journal Issue
4
Pages
453-463
Date Issued
2014
Author(s)
Abstract
Osteosarcoma is the most common primary malignancy of bone and is characterized by a high malignant and metastatic potential. Transforming growth factor alpha (TGF-α) is classified as the EGF (epidermal growth factor)-like family, which is involved in cancer cellular activities such as proliferation, motility, migration, adhesion and invasion abilities. However, the effect of TGF-α on human osteosarcoma is largely unknown. We found that TGF-α increased the cell migration and expression of intercellular adhesion molecule-1 (ICAM-1) in human osteosarcoma cells. Transfection of cells with ICAM-1 siRNA reduced TGF-α-mediated cell migration. We also found that the phosphatidylinositol 3′-kinase (PI3K)/Akt/NF-κB pathway was activated after TGF-α treatment, and TGF-α-induced expression of ICAM-1 and cell migration was inhibited by the specific inhibitors and siRNAs of PI3K, Akt, and NF-κB cascades. In addition, knockdown of TGF-α expression markedly decreased cell metastasis in vitro and in vivo. Our results indicate that TGF-α/EGFR interaction elicits PI3K and Akt activation, which in turn activates NF-κB, resulting in the expression of ICAM-1 and contributing the migration of human osteosarcoma cells. ? 2014 Elsevier Inc.
SDGs
Other Subjects
intercellular adhesion molecule 1; phosphatidylinositol 3 kinase; protein kinase B; transforming growth factor alpha; animal experiment; article; cell migration; human; human cell; human cell culture; in vitro study; in vivo study; male; metastasis; mouse; nonhuman; osteosarcoma; osteosarcoma cell line; priority journal; protein expression; signal transduction; tumor xenograft; Migration; Osteosarcoma; TGF-α; Animals; Antineoplastic Agents; Bone Neoplasms; Cell Line, Tumor; Cell Movement; Humans; Intercellular Adhesion Molecule-1; Lung Neoplasms; Male; Mice; Mice, SCID; NF-kappa B; Osteosarcoma; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Receptor, Epidermal Growth Factor; Recombinant Proteins; RNA Interference; Second Messenger Systems; Transforming Growth Factor alpha; Tumor Burden; Up-Regulation; Xenograft Model Antitumor Assays
Publisher
Elsevier Inc.
Type
journal article