Muc-1 promotes migration and invasion of oral squamous cell carcinoma cells via PI3K-Akt signaling

Int J Clin Exp Pathol. 2015 Sep 1;8(9):10365-74. eCollection 2015.

Abstract

Muc-1 is a member of the carbohydrate-binding protein family that contributes to neoplastic transformation, tumor survival, angiogenesis, and metastasis. The aim of this study is to investigate the role of muc-1 in human oral squamous cell carcinoma progression. In this study, we tested our hypothesis that muc-1 regulate oral squamous cell carcinoma cells (SCC-9) malignant biological behaviors, and silencing muc-1 reduced SCC-9 cellular colony forming ability, migration and invasion. Moreover, silenced cells present defects in phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (Akt) signaling, and reduced expression/activity of matrix metallopeptidase (MMP)-2/9. Furthermore, in muc-1 siRNA-transfected cells, we detected a decrease in signal transducer and activator of transcription 3 (STAT3) phosphorylation and nuclear translocation. In vivo, muc-1 siRNA cells inoculated subcutaneously in nude mice demonstrated decreased tumor growth and PI3K-Akt signaling inhibition. These results indicate that muc-1 is a key factor in SCC-9 tumor migration, invasion, and suggesting that muc-1 can be a novel therapeutic target in oral squamous cell carcinoma.

Keywords: Muc-1; Oral squamous cell carcinoma; RNA interference; tumor invasion.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Cell Proliferation / physiology
  • Humans
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Nude
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Mucin-1 / metabolism*
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / physiology*

Substances

  • MUC1 protein, human
  • Mucin-1
  • STAT3 Transcription Factor
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9