Pinin facilitated proliferation and metastasis of colorectal cancer through activating EGFR/ERK signaling pathway

Oncotarget. 2016 May 17;7(20):29429-39. doi: 10.18632/oncotarget.8738.

Abstract

Increasing emphasis has been put on the influence of desmosome related proteins on progress of colorectal cancer (CRC). Pinin (PNN) is a desmosome-associated molecule that has been reported its overexpression could increase desmoglein 2 (DSG2) and E-cadherin (E-ca) levels. However, it was documented that DSG2 and E-ca had opposite functions in CRC. Thus, we attempted to elucidate function and mechanism of PNN in CRC. Herein, we revealed that overexpression of PNN was significantly correlated with the aggressive characteristics and indicated poor overall survival of CRC patients. In addition, the proliferation, invasion in vitro, and tumorigenic growth, metastasis in vivo were also promoted by the up-regulation of PNN. It was also verified that up-regulation of PNN increased the expression of DSG2 and activated the EGFR/ERK signaling pathway. Our findings suggested that PNN, as a valuable marker of prognosis, has important influence on the progression of CRC.

Keywords: EGFR/ERK; PNN; colorectal cancer; metastasis.

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • ErbB Receptors / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Heterografts
  • Humans
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness / pathology
  • Nuclear Proteins / metabolism*
  • Prognosis
  • Signal Transduction / physiology

Substances

  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • Nuclear Proteins
  • PNN protein, human
  • EGFR protein, human
  • ErbB Receptors
  • Extracellular Signal-Regulated MAP Kinases