title: A suppressive role of mitogen inducible gene-2 in mesenchymal cancer cell invasion.
abstract: Cancer cell invasion of extracellular matrix (ECM) is essential for dissemination of cancer cells and metastasis. In this study, we have investigated the role of mitogen inducible gene-2 (Mig-2, also known as kindlin-2), a focal adhesion protein whose expression is altered in several types of human cancers, in mesenchymal cancer cell invasion. Mig-2 is abundantly expressed in SK-LMS-1 leiomyosarcoma cells. The level of Mig-2, however, is considerably lower in more invasive HT-1080 fibrosarcoma cells. Overexpression of Mig-2 in HT-1080 and SK-LMS-1 cells substantially reduced their ability to invade ECM in an in vitro Matrigel invasion assay. Conversely, knockdown of Mig-2 markedly increased the invasiveness of these cells. Consistent with a suppressive role in mesenchymal cancer cell invasion, Mig-2 inhibits urokinase-type plasminogen activator (uPA) secretion and pericellular proteolysis. Overexpression of Mig-2 increased uPA accumulation at the intracellular face of cell-ECM adhesions and reduced the level of secreted uPA. Conversely, knockdown of Mig-2 reduced uPA accumulation at the intracellular face of cell-ECM adhesions and increased uPA secretion. Our results reveal an important role of Mig-2 in suppression of mesenchymal cancer cell invasion and shed new light on how altered Mig-2 expression could influence cancer cell invasion.
authors.affiliation: 707B Scaife Hall, Department of Pathology, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Shi
authors.forename: Chuanyue
authors.initials: C
authors.lastname: Wu
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D005109:Extracellular Matrix / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007890:Leiomyosarcoma / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: C477322:FERMT3 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D014568:Urokinase-Type Plasminogen Activator