title: CD44 variant, but not standard CD44 isoforms, mediate disassembly of endothelial VE-cadherin junction on metastatic melanoma cells.
abstract: Loss of endothelial adherens junctions is involved in tumor metastasis. Here, we demonstrate that, in the metastatic Lu1205 melanoma cells, expression of the CD44 variant CD44v8-v10 induced junction disassembly and vascular endothelial (VE)-cadherin phosphorylation at Y658 and Y731. Short interfering RNA (siRNA)-mediated CD44 knockdown or sialic acid cleavage reversed these effects. Moreover, microspheres coated with recombinant CD44v8-v10 promoted endothelial junction disruption. Overexpression of CD44v8-v10 but not of standard CD44 (CD44s) promoted gap formation in the non-metastatic WM35 melanoma cells, whereas CD44 knockdown or neuraminidase treatment dramatically diminished melanoma transendothelial migration. Endothelial cells transfected with the phosphomimetic VE-cadherin mutant Y658E supported transmigration of CD44-silenced Lu1205 cells. Our findings imply that CD44 variant isoform (CD44v) but not CD44s regulates endothelial junction loss, promoting melanoma extravasation.
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China; Department of Bioengineering, Pennsylvania State University, University Park, PA 16801, USA.
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Bioengineering, Pennsylvania State University, University Park, PA 16801, USA.
authors.forename: Changliang
authors.initials: C
authors.lastname: Fu
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Bai
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Erqun
authors.initials: E
authors.lastname: Song
authors.forename: Cheng
authors.initials: C
authors.lastname: Dong
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China. Electronic address: ysong@swu.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D042783:Endothelial Cells / Q000473:pathology*; D055785:Gene Knockdown Techniques; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000473:pathology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D020033:Protein Isoforms / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D015820:Cadherins; D018960:Hyaluronan Receptors; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D019158:N-Acetylneuraminic Acid
keywords: Adherens junction; CD44 variant isoform; Short interfering RNA; Tumor metastasis; VE-cadherin phosphorylation