title: The cell adhesion molecule L1 promotes gallbladder carcinoma progression in vitro and in vivo.
abstract: Recent studies have demonstrated that the cell adhesion molecule, L1, is expressed in several malignant tumor types and its expression correlates with tumor progression and metastasis. However, the role of L1 in gallbladder carcinoma (GBC) remains unclear. Here, we demonstrate that L1 is expressed in GBC cells and plays an important role in the growth, motility, invasiveness, and adhesiveness of GBC cells. Specific depletion or overexpression of L1 in the GBC cell lines JCRB1033 and SNU-308, respectively, was achieved by lentivirus-mediated transduction and expression of an L1 mRNA-specific short hairpin RNA or full-length human L1. Stable depletion of L1 led to a significant decrease in GBC cell proliferation, migration and invasion, as well as decreased intracellular signaling through AKT and FAK. Overexpression of L1 in GBC cells enhanced these cellular activities. In a GBC xenograft nude mouse model, suppression of L1 markedly reduced tumor growth and increased the survival of tumor-bearing mice whereas L1 overexpression stimulated tumorigenicity. Taken together, these results suggest that L1 plays a crucial role in GBC progression and may be a novel therapeutic target in GBC treatment.
authors.affiliation: Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, 52 Eoeun-dong, Yuseong-gu, Daejeon 305-333, Republic of Korea.
authors.forename: Juyeon
authors.initials: J
authors.lastname: Jung
authors.forename: Yeon Sung
authors.initials: YS
authors.lastname: Son
authors.forename: Hongryeol
authors.initials: H
authors.lastname: Park
authors.forename: Seong Kook
authors.initials: SK
authors.lastname: Jeon
authors.forename: Jung Whoi
authors.initials: JW
authors.lastname: Lee
authors.forename: Song-Yi
authors.initials: SY
authors.lastname: Choi
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Young-Guen
authors.initials: YG
authors.lastname: Kwon
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Hong
authors.forename: Jeong-Ki
authors.initials: JK
authors.lastname: Min
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D005706:Gallbladder Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D039842:Neural Cell Adhesion Molecule L1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D039842:Neural Cell Adhesion Molecule L1; D034741:RNA, Small Interfering; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt