Expression of SLP-2 was associated with invasion of esophageal squamous cell carcinoma

PLoS One. 2013 May 8;8(5):e63890. doi: 10.1371/journal.pone.0063890. Print 2013.

Abstract

Introduction: Stomatin-like protein 2 (SLP-2), a member of the Stomatin superfamily, has been identified as an oncogenic-related protein and found to be up-regulated in multi-cancers. Nonetheless, the expression pattern and regulation of SLP-2 in human esophageal squamous cell carcinoma (ESCC) remain unexplored.

Methods: Immunohistochemistry and immunofluorescence staining analysis were performed to show SLP-2 expression and location. RNAi method was used to inhibit specific protein expression. Transwell assay was done to investigate cells invasive capability. RT-PCR and Western blot analysis were used to detect mRNA and protein expression levels.

Results: Immunohistochemical analysis showed that up-regulation of SLP-2 was found in invasive front compared with cancer central tissue in ESCC. Inhibition of SLP-2 by SLP-2 siRNA can decrease ESCC cells invasive capability through MMP-2 dependent manner. Up-regulation of SLP-2 was effectively abrogated by the ERK1/2 inhibitors either PD98059 or U0126, but no effect was showed by the treatment of AKT inhibitors either LY294002 or MK-2206. So the regulation of SLP-2 was involved in activation of the MAPK/ERK pathway.

Conclusions: We found that PMA/EGF could induce the up-regulated expression of SLP-2 probably through activating ERK signalling. The current study suggests that SLP-2 may represent an important molecular hallmark that is clinically relevant to the invasion of ESCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Proteins / metabolism*
  • Blotting, Western
  • Butadienes
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / physiopathology
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / physiopathology
  • Flavonoids
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Immunohistochemistry
  • MAP Kinase Signaling System / physiology
  • Membrane Proteins / metabolism*
  • Neoplasm Invasiveness / physiopathology*
  • Nitriles
  • RNA Interference

Substances

  • Blood Proteins
  • Butadienes
  • Flavonoids
  • Membrane Proteins
  • Nitriles
  • STOML2 protein, human
  • U 0126
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Grants and funding

This work was partially supported by the grant: Subject of Science and Technology Development Fund of Tianjin Education Commission (20060108), Tianjin Municipal Science and Technology Commission Research Fund (10JCYBJC14100), Tianjin Medical University Cancer Hospital Research Funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.