title: Dual mechanisms of action of the RNA-binding protein human antigen R explains its regulatory effect on melanoma cell migration.
abstract: Overexpression of wingless-type MMTV integration site family 5A (WNT5A) plays a significant role in melanoma cancer progression; however, the mechanism(s) involved remains unknown. In breast cancer, the human antigen R (HuR) has been implicated in the regulation of WNT5A expression. Here, we demonstrate that endogenous expression of WNT5A correlates with levels of active HuR in HTB63 and WM852 melanoma cells and that HuR binds to WNT5A messenger RNA in both cell lines. Although the HuR inhibitor MS-444 significantly impaired migration in both melanoma cell lines, it reduced WNT5A expression only in HTB63 cells, as did small interfering RNA knockdown of HuR. Consistent with this finding, MS-444-induced inhibition of HTB63 cell migration was restored by the addition of recombinant WNT5A, whereas MS-444-induced inhibition of WM852 cell migration was restored by the addition of recombinant matrix metalloproteinase-9, another HuR-regulated protein. Clearly, HuR positively regulates melanoma cell migration via at least 2 distinct mechanisms making HuR an attractive therapeutic target for halting melanoma dissemination.
authors.affiliation: Cell and Experimental Pathology, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Moradi
authors.affiliation: Cell and Experimental Pathology, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Pontus
authors.initials: P
authors.lastname: Berglund
authors.affiliation: Cell and Experimental Pathology, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Rickard
authors.initials: R
authors.lastname: Linnskog
authors.affiliation: Center for Molecular Pathology, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Leandersson
authors.affiliation: Cell and Experimental Pathology, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Tommy
authors.initials: T
authors.lastname: Andersson
authors.affiliation: Cell and Experimental Pathology, Department of Translational Medicine, Lund University, Malmö, Sweden. Electronic address: Chandra.Prasad@med.lu.se.
authors.forename: Chandra Prakash
authors.initials: CP
authors.lastname: Prasad
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism*; D005663:Furans / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008954:Models, Biological; D008970:Molecular Weight; D009284:Naphthols / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D000071818:Wnt-5a Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000067780:ELAV-Like Protein 1; D005663:Furans; D009284:Naphthols; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000071818:Wnt-5a Protein; C096620:5,8-dihydroxy-3-methyl-4-(9H)-naphtho(2,3-c)furanone; D020780:Matrix Metalloproteinase 9