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ADAM9 Isoforms in Breast Cancer Cell Migration
Author(s) -
Fry Jessica Lynn,
Toker Alex
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.523.1
Subject(s) - cell migration , biology , cancer research , microbiology and biotechnology , disintegrin , matricellular protein , integrin , cell , cancer cell , metalloproteinase , cancer , extracellular matrix , matrix metalloproteinase , genetics
Tumor cell migration is a complex event mediated by the genetic characteristics of the tumor cells themselves in cooperation with changes in the tissue microenvironment. ADAM9, a member of a family of transmembrane matrix‐metalloproteases named for their integrin‐binding D isintegrin A nd M etalloprotease domains, is implicated in cell‐cell and cell‐matrix interactions as well as in shedding of receptors and ligands. ADAM9 is present in breast cancer cell lines as two alternatively spliced isoforms ‐‐ ADAM9‐L and the truncated, secreted, ADAM9‐S. Exogenous and endogenous overexpression of ADAM9‐S increases breast cancer cell migration, leading to our hypothesis that ADAM9 present in the breast tumor environment mediates tumor cell migration via an unknown mechanism. Using lentiviral‐shRNA constructs, we have silenced expression of endogenous human ADAM9 protein in the BT549 and CAMA‐1 breast cancer cell lines, resulting in an increase in cell migration measured by transwell assay. This enhanced migration is reversed by reintroduction of ADAM9‐L protein into these cells, while reintroduction of ADAM9‐S enhances this migration phenotype in a metalloprotease‐dependent manner. Further analysis using functional mutants of the metalloprotease, disintegrin, and cytoplasmic signaling domains of ADAM9‐L will lend insight into the mechanisms by which ADAM9 mediates breast cancer cell migration.