Desmoglein 2 depletion leads to increased migration and upregulation of the chemoattractant secretoneurin in melanoma cells

PLoS One. 2014 Feb 18;9(2):e89491. doi: 10.1371/journal.pone.0089491. eCollection 2014.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bromodeoxyuridine
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Desmoglein 2 / deficiency
  • Desmoglein 2 / metabolism*
  • Electric Impedance
  • Gene Expression Profiling
  • Gene Expression Regulation / physiology*
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Melanoma / physiopathology*
  • Microscopy, Fluorescence
  • RNA Interference
  • Radioimmunoassay
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Secretogranin II / metabolism


  • Desmoglein 2
  • Secretogranin II
  • Bromodeoxyuridine

Grant support

This work was supported by grants from the Deutsche Krebshilfe to WK Peitsch (project no. 108626) and to JU (project no. 109312) and a grant from the Deutsche Forschungsgemeinschaft (DFG) to SWS (SFB/TR23, project A9). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.