PMID- 26503469 OWN - NLM STAT- MEDLINE DCOM- 20160922 LR - 20181202 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 6 IP - 38 DP - 2015 Dec 1 TI - Amphiregulin enhances intercellular adhesion molecule-1 expression and promotes tumor metastasis in human osteosarcoma. PG - 40880-95 LID - 10.18632/oncotarget.5679 [doi] AB - 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-kappaB 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. FAU - Liu, Ju-Fang AU - Liu JF AD - Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Tsao, Ya-Ting AU - Tsao YT AD - Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan. FAU - Hou, Chun-Han AU - Hou CH AD - Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (AREG protein, human) RN - 0 (Amphiregulin) RN - 0 (EGF Family of Proteins) RN - 0 (ICAM1 protein, human) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Amphiregulin MH - Animals MH - Apoptosis MH - Blotting, Western MH - Bone Neoplasms/genetics/metabolism/*pathology MH - Cell Movement MH - Cell Proliferation MH - Chromatin Immunoprecipitation MH - EGF Family of Proteins/genetics/*metabolism MH - ErbB Receptors/genetics/metabolism MH - Humans MH - Immunoenzyme Techniques MH - Intercellular Adhesion Molecule-1/chemistry/genetics/*metabolism MH - Lung Neoplasms/genetics/metabolism/*secondary MH - Male MH - Mice MH - Mice, SCID MH - NF-kappa B/genetics/metabolism MH - Osteosarcoma/genetics/metabolism/*pathology MH - Phosphatidylinositol 3-Kinases/genetics/metabolism MH - RNA, Messenger/genetics MH - RNA, Small Interfering/genetics MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction MH - Tumor Cells, Cultured MH - Xenograft Model Antitumor Assays PMC - PMC4747375 OTO - NOTNLM OT - EGFR OT - ICAM-1 OT - amphiregulin OT - cell migration OT - osteosarcoma metastasis COIS- CONFLICTS OF INTEREST The authors state no conflict of interest. EDAT- 2015/10/28 06:00 MHDA- 2016/09/23 06:00 PMCR- 2015/12/01 CRDT- 2015/10/28 06:00 PHST- 2015/05/21 00:00 [received] PHST- 2015/09/13 00:00 [accepted] PHST- 2015/10/28 06:00 [entrez] PHST- 2015/10/28 06:00 [pubmed] PHST- 2016/09/23 06:00 [medline] PHST- 2015/12/01 00:00 [pmc-release] AID - 5679 [pii] AID - 10.18632/oncotarget.5679 [doi] PST - ppublish SO - Oncotarget. 2015 Dec 1;6(38):40880-95. doi: 10.18632/oncotarget.5679.