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RANKL increases migration of human lung cancer cells through intercellular adhesion molecule‐1 up‐regulation
Author(s) -
Chen LiMien,
Kuo ChiaHua,
Lai TungYuan,
Lin YuehMin,
Su ChengChuan,
Hsu HisHsien,
Tsai FuuJen,
Tsai ChangHai,
Huang ChihYang,
Tang ChihHsin
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23009
Subject(s) - rankl , mapk/erk pathway , microbiology and biotechnology , cancer research , cell migration , a549 cell , cell adhesion , cancer cell , chemistry , signal transduction , receptor , activator (genetics) , biology , cell , cancer , biochemistry , genetics
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.