The transcription factor Snail enhanced the degradation of E-cadherin and desmoglein 2 in oral squamous cell carcinoma cells.

Abstract

Epithelial-mesenchymal transition (EMT), a key process in the tumor metastatic cascade, is characterized by the loss of cell-cell junctions and cell polarity as well as the acquisition of migratory and invasive properties. However, the precise molecular events that initiate this complex EMT process are poorly understood. Snail is a regulator of EMT that represses E-cadherin transcription through its interaction with proximal E-boxes in the promoter region of target genes. To investigate the role of Snail in EMT, we generated stable Snail transfectants using the oral squamous cell carcinoma cell line HSC-4 (Snail/HSC-4). Snail/HSC-4 cells had a spindle-shaped mesenchymal morphology, and enhanced migration and invasiveness relative to control cells. Consistent with these EMT changes, the downregulation of epithelial marker proteins, E-cadherin and desmoglein 2, and the upregulation of mesenchymal marker proteins, vimentin and N-cadherin were detected. Despite these observations, the mRNA levels of E-cadherin and desmoglein 2 did not decrease significantly. Although E-cadherin and desmoglein 2 proteins were stable in parental HSC-4 cells, these proteins were rapidly degraded in Snail/HSC-4 cells. The degradation of E-cadherin, but not desmoglein 2, was inhibited by dynasore, an inhibitor of dynamin-dependent endocytosis. Therefore, in HSC-4 cells Snail regulates levels of these proteins both transcriptionally and post-translationally.

• Authors: Kenichi Kume, Misako Haraguchi, Hiroshi Hijioka, Takayuki Ishida, Akihiko Miyawaki, Norifumi Nakamura, Masayuki Ozawa
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 430 Issue 3 Pg. 889-94 (Jan 18 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 23261431 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Cadherins
• Desmoglein 2
• Hydrazones
• N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide
• Snail Family Transcription Factors
• Transcription Factors

Topics

• Cadherins (metabolism)
• Carcinoma, Squamous Cell (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement
• Desmoglein 2 (metabolism)
• Endocytosis (drug effects)
• Epithelial-Mesenchymal Transition
• Humans
• Hydrazones (pharmacology)
• Mouth Neoplasms (metabolism, pathology)
• Neoplasm Invasiveness
• Proteolysis
• Snail Family Transcription Factors
• Transcription Factors (genetics, metabolism)
• Up-Regulation