CD44 variant, but not standard CD44 isoforms, mediate disassembly of endothelial VE‐cadherin junction on metastatic melanoma cells. Issue 24 (4th November 2014)

• Record Type: Journal Article
• Authors: Zhang, Pu; Fu, Changliang; Bai, Huiyuan; Song, Erqun; Song, Yang
• Is Part Of: FEBS letters. Volume 588:Issue 24(2014)
• Page Start: 4573
• Page End: 4582
• Publication Date: 2014-11-04
• Subjects: HUVEC -- human umbilical vein endothelial cell -- EC -- endothelial cell -- CD44v -- CD44 variant isoform -- CD44s -- CD44 standard isoform -- TC -- tumor cell -- VE-cadherin -- vascular endothelial-cadherin -- TCM -- tumor conditioned medium -- siRNA -- short interfering RNA -- DAPI -- 4′, 6-diamidino-2-phenylindole -- PBS -- phosphate buffered saline -- EGFP -- enhanced green fluorescence protein -- RTK -- receptor tyrosine kinase -- DMJ -- deoxymannojirimycin -- benzyl-GalNAc -- benzyl-2-acetamido-2-deoxy-a-d-galactopyranoside -- CD44 variant isoform -- Tumor metastasis -- VE-cadherin phosphorylation -- Short interfering RNA -- Adherens junction; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.10.027
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : Melanoma contact induced VE‐cadherin phosphorylation and endothelial gap formation. Lu1205 melanoma cell expresses high levels of CD44v8‐v10. CD44v8‐v10 but not CD44s facilitated Lu1205‐induced endothelial gap formation. CD44v8‐v10 overexpression enhanced the ability of WM35 to induce junction loss. CD44 knockdown suppressed VE‐cadherin disassembly‐dependent Lu1205 extravasation.