title: Hic-5 affects proliferation, migration and invasion of B16 murine melanoma cells.
abstract: Hic-5 is a shuttling protein between the cell membrane and the nucleus which functions as a focal adhesion adaptor protein and a nuclear receptor coactivator. Although several studies have shown its involvement in other types of cancer, the role of Hic-5 in melanoma is unknown. Herein, we show for the first time that Hic-5 is expressed in B16-F1 murine melanoma cells. To determine its function in melanoma cells, we used shRNA-mediated RNA interference and established stable clones with down-regulated Hic-5 expression. These clones had impaired growth and metastatic potential compared with controls in vivo, which correlated with decreased proliferation, migration and invasion in vitro. Moreover, silencing of Hic-5 expression in B16-F1 activated RhoA with an amoeboid phenotypic change, indicating that Hic-5 is a key regulator of B16-F1 metastasis in the context of Rho-dependent motility. These results provide new evidence that Hic-5 is a possible molecular target for treatment of melanoma.
authors.affiliation: Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Fumihito
authors.initials: F
authors.lastname: Noguchi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Inui
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Itami
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D048430:Cell Shape; D002999:Clone Cells; D003094:Collagen; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D004338:Drug Combinations; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D007279:Injections, Subcutaneous; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D007797:Laminin; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011509:Proteoglycans; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016019:Survival Analysis; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D060588:LIM Domain Proteins; D007797:Laminin; D011509:Proteoglycans; C090090:Tgfb1i1 protein, mouse; C059485:matrigel; D003094:Collagen; D020742:rhoA GTP-Binding Protein