title: Desmoglein 2 depletion leads to increased migration and upregulation of the chemoattractant secretoneurin in melanoma cells.
abstract: During development and progression of malignant melanoma, an important role has been attributed to alterations of cell-cell adhesions, in particular, to a "cadherin switch" from E- to N-cadherin. We have previously shown that a subtype of melanoma cells express the desmosomal cadherin desmoglein 2 as non-junction-bound cell surface protein in addition to classical cadherins. To study the role of desmoglein 2 in melanoma cells, melanoma lines containing high endogenous amounts of desmoglein 2 were depleted of the protein by RNA interference. Transwell migration and scratch wounding assays showed markedly increased migration upon desmoglein 2 suppression whereas proliferation and viability remained unaltered. In gene expression profiles, desmoglein 2 depletion was associated with overexpression of migration-related genes. Strongest overexpression was found for secretogranin II which has not been reported in melanoma cells before. The bioactive peptide derived from secretogranin II, secretoneurin, is known to exert chemoattractive functions and was demonstrated here to stimulate melanoma cell migration. In summary, we show that desmoglein 2 expression attenuates migration of melanoma cells. The mechanism of desmoglein 2 impaired cell migration is mediated by downregulation of secretogranin II. Loss of desmoglein 2 increases expression of secretogranin II, followed by an enhanced migratory activity of melanoma cells. Our data add a new pathway of regulating melanoma cell migration related to a desmoglein 2-secretogranin II axis.
authors.affiliation: Department of Dermatology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany ; Helmholtz Group for Cell Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Wiebke K
authors.initials: WK
authors.lastname: Peitsch
authors.affiliation: Department of Dermatology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany ; Helmholtz Group for Cell Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Doerflinger
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Reiner
authors.initials: R
authors.lastname: Fischer-Colbrie
authors.affiliation: Department of Dermatology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Huck
authors.affiliation: Department of Dermatology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Bauer
authors.affiliation: Department of Dermatology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany ; Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Utikal
authors.affiliation: Department of Dermatology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Sergij
authors.initials: S
authors.lastname: Goerdt
authors.affiliation: Department of Dermatology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Schneider
mesh_terms: D001973:Bromodeoxyuridine; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D051301:Desmoglein 2 / Q000172:deficiency / Q000378:metabolism*; D017097:Electric Impedance; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008545:Melanoma / Q000503:physiopathology*; D008856:Microscopy, Fluorescence; D034622:RNA Interference; D011863:Radioimmunoassay; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053381:Secretogranin II / Q000378:metabolism
chemical_list: D051301:Desmoglein 2; D053381:Secretogranin II; D001973:Bromodeoxyuridine