title: RANKL-induced migration of MDA-MB-231 human breast cancer cells via Src and MAPK activation.
abstract: Accumulating studies have shown that the receptor activator of nuclear factor-κB ligand (RANKL)/RANK pathway plays an important role in tumor metastasis. However, the involvement of the RANKL/RANK signal transduction pathway in breast cancer metastasis remains unclear. The present study, therefore, investigated the role of downstream molecules of RANKL/RANK signaling in breast cancer cells using Transwell chemotaxis assays. RANKL was shown to direct the migration of MDA-MB-231 breast cancer cells. Osteoprotegerin (OPG; soluble decoy receptor of RANKL) inhibited RANKL-induced migration. RANKL activated Src kinase in MDA-MB-231 cells, as shown by Western blotting, and pretreatment with a Src inhibitor abrogated RANKL-induced cell migration, in a similar manner to OPG. Short-hairpin RNA against RANK, delivered via a lentiviral vector, significantly abolished the expression of phosphorylated Src. Stimulation by RANKL induced the phosphorylation of mitogen-activated protein kinases (MAPKs) (ERK, p38, JNK), and specific inhibitors of MAPKs blocked RANKL-induced cell migration. Furthermore, the expression of phosphorylated MAPKs could be blocked by a Src inhibitor and by small interfering RNA against Src. These findings suggest that Src and MAPK pathways may be involved in RANKL-induced MDA-MB-231 breast cancer cell migration.
authors: Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors: Zhen-Ning
authors: ZN
authors: Tang
authors: Fan
authors: F
authors: Zhang
authors: Peng
authors: P
authors: Tang
authors: Xiao-Wei
authors: XW
authors: Qi
authors: Jun
authors: J
authors: Jiang
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009362:Neoplasm Metastasis; D010010:Osteoclasts / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D053245:RANK Ligand; D034741:RNA, Small Interfering; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases