title: L1 cell adhesion molecule induces melanoma cell motility by activation of mitogen-activated protein kinase pathways.
abstract: L1 cell adhesion molecule (L1CAM) is highly expressed in various types of cancer cells and has been implicated in the control of cell proliferation and motility. Recently, L1CAM was reported to induce the motility of melanoma cells, but the mechanism of this induction remains poorly understood. In this study, we investigated the molecular mechanisms by which L1CAM induces the motility of melanoma cells. Unlike other types of cancer cells, B16F10 melanoma cells highly expressed L1CAM at both the RNA and protein levels, and the expression of L1CAM induced AP-1 activity. In accordance to AP-1 activation, MAPK signaling pathways were activated by L1CAM. Inhibition of L1CAM expression by L1CAM-specific siRNA suppressed the activation of MAPKs such as ERK and p38. However, no significant change was observed in JNK activation. As expected, upstream MAP2K, MKK3/6, MAP3K, and TAK1 were also deactivated by the inhibition of L1CAM expression. L1CAM induced the motility of B16F10 cells. Inhibition of L1CAM expression suppressed migration and invasion of B16F10 cells, but no suppressive effect was observed on their proliferation and anti-apoptotic resistance. Treatment of B16F10 cells with U0126, an ERK inhibitor, or SB203580, a p38 inhibitor, suppressed the migration and invasion abilities of B16F10 cells. Taken together, our results suggest that L1CAM induces the motility of B16F10 melanoma cells via the activation of MAPK pathways. This finding provides a more detailed molecular mechanism of L1CAM-mediated induction of melanoma cell motility.
authors: Young-Su
authors: YS
authors: Yi
authors: Kwang-Soo
authors: KS
authors: Baek
authors: Jae Youl
authors: JY
authors: Cho
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008156:Luciferases / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008545:Melanoma / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D039842:Neural Cell Adhesion Molecule L1 / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000235:genetics; D014162:Transfection
chemical_list: D039842:Neural Cell Adhesion Molecule L1; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases