RANKL increases migration of human lung cancer cells through intercellular adhesion molecule-1 up-regulation

✍ Scribed by Li-Mien Chen; Chia-Hua Kuo; Tung-Yuan Lai; Yueh-Min Lin; Cheng-Chuan Su; His-Hsien Hsu; Fuu-Jen Tsai; Chang-Hai Tsai; Chih-Yang Huang; Chih-Hsin Tang

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 381 KB
• Volume: 112
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.23009

✦ Synopsis

Abstract

Invasion of distant tissues by tumor cells is the primary cause of therapeutic failure in the treatment of malignant lung cancer cells. Receptor activator of nuclear factor‐κB ligand (RANKL) and its receptor, RANK, play a key role in osteoclastogenesis and tumor metastasis. Intercellular adhesion molecule‐1 (ICAM‐1, also called CD54), a member of the immunoglobulin supergene family, is an inducible surface glycoprotein that mediates adhesion‐dependent cell‐to‐cell interactions. The effects of RANKL on cell migration and ICAM‐1 expression in human lung cancer cells are largely unknown. We found that RANKL directed the migration and increased ICAM‐1 expression in human lung cancer (A549) cells. Pretreatment of A549 cells with the MAPK kinase (MEK) inhibitor PD98059 or U0126 inhibited RANKL‐mediated migration and ICAM‐1 expression. Stimulation of cells with RANKL increased the phosphorylation of MEK and extracellular signal‐regulating kinase (ERK). In addition, an NF‐κB inhibitor (PDTC) and IκB protease inhibitor (TPCK) also inhibited RANKL‐mediated cell migration and ICAM‐1 up‐regulation. Taken together, these results suggest that the RANKL and RANK interaction acts through MEK/ERK, which in turn activates NF‐κB, resulting in the activation of ICAM‐1 and contributing to the migration of human lung cancer cells. J. Cell. Biochem. 112: 933–941, 2011. © 2010 Wiley‐Liss, Inc.