Open AccessAmphiregulin enhances intercellular adhesion molecule-1 expression and promotes tumor metastasis in human osteosarcoma
Author(s) -
Ju-Fang Liu,
Ya Ting Tsao,
ChunHan Hou
Publication year - 2015
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.5679
Subject(s) - amphiregulin , osteosarcoma , cancer research , metastasis , pi3k/akt/mtor pathway , gene silencing , protein kinase b , medicine , cancer , biology , signal transduction , epidermal growth factor receptor , microbiology and biotechnology , biochemistry , gene
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.