title: ALCAM regulates motility, invasiveness, and adherens junction formation in uveal melanoma cells.
abstract: ALCAM, a member of the immunoglobulin superfamily, has been implicated in numerous developmental events and has been repeatedly identified as a marker for cancer metastasis. Previous studies addressing ALCAM's role in cancer have, however, yielded conflicting results. Depending on the tumor cell type, ALCAM expression has been reported to be both positively and negatively correlated with cancer progression and metastasis in the literature. To better understand how ALCAM might regulate cancer cell behavior, we utilized a panel of defined uveal melanoma cell lines with high or low ALCAM levels, and directly tested the effects of manipulating these levels on cell motility, invasiveness, and adhesion using multiple assays. ALCAM expression was stably silenced by shRNA knockdown in a high-ALCAM cell line (MUM-2B); the resulting cells displayed reduced motility in gap-closure assays and a reduction in invasiveness as measured by a transwell migration assay. Immunostaining revealed that the silenced cells were defective in the formation of adherens junctions, at which ALCAM colocalizes with N-cadherin and ß-catenin in native cells. Additionally, we stably overexpressed ALCAM in a low-ALCAM cell line (MUM-2C); intriguingly, these cells did not exhibit any increase in motility or invasiveness, indicating that ALCAM is necessary but not sufficient to promote metastasis-associated cell behaviors. In these ALCAM-overexpressing cells, however, recruitment of ß-catenin and N-cadherin to adherens junctions was enhanced. These data confirm a previously suggested role for ALCAM in the regulation of adherens junctions, and also suggest a mechanism by which ALCAM might differentially enhance or decrease invasiveness, depending on the type of cadherin adhesion complexes present in tissues surrounding the primary tumor, and on the cadherin status of the tumor cells themselves.
authors: Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America.
authors: Karry M
authors: KM
authors: Jannie
authors: Christopher S
authors: CS
authors: Stipp
authors: Joshua A
authors: JA
authors: Weiner
mesh_terms: D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000235:genetics / Q000378:metabolism*; D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014604:Uveal Neoplasms / Q000235:genetics / Q000378:metabolism*; D000098943:Uveal Melanoma
chemical_list: D020410:Activated-Leukocyte Cell Adhesion Molecule