WIP1 stimulates migration and invasion of salivary adenoid cystic carcinoma by inducing MMP-9 and VEGF-C

Oncotarget. 2015 Apr 20;6(11):9031-44. doi: 10.18632/oncotarget.3320.

Abstract

The wild-type p53 induced phosphatase 1 (WIP1) is an oncogene overexpressed in a variety of human cancers. Here, we demonstrated that WIP1 silencing reduced MMP-9 and VEGF-C expression as well as migration and invasion of salivary adenoid cystic carcinoma (ACC) cells. Overexpression of MMP-9 or VEGF-C restored migration and invasion in WIP1 knockdown cells, indicating that MMP-9 and VEGF-C are downstream targets of WIP1 signaling. Levels of cyclin D1 and c-Myc, targets of Wnt/β-catenin pathway, were significantly decreased by WIP1 silencing. In addition, WIP1 expression was positively associated with metastasis and prognosis of ACC patients as well as with MMP-9 or VEGF-C in ACC tissues.

Keywords: adenoid cystic carcinoma (ACC); invasion; metastasis; salivary gland; wild-type p53 induced phosphatase 1 (WIP1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Adenoid Cystic / metabolism
  • Carcinoma, Adenoid Cystic / mortality
  • Carcinoma, Adenoid Cystic / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • DNA, Complementary / genetics
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Heterografts
  • Humans
  • Kaplan-Meier Estimate
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase 9 / genetics
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / physiology*
  • Prognosis
  • Proportional Hazards Models
  • Protein Phosphatase 2C
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Random Allocation
  • Recombinant Fusion Proteins / metabolism
  • Salivary Gland Neoplasms / metabolism
  • Salivary Gland Neoplasms / mortality
  • Salivary Gland Neoplasms / pathology*
  • Signal Transduction
  • Transduction, Genetic
  • Transfection
  • Vascular Endothelial Growth Factor C / biosynthesis*
  • Vascular Endothelial Growth Factor C / genetics

Substances

  • DNA, Complementary
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • VEGFC protein, human
  • Vascular Endothelial Growth Factor C
  • PPM1D protein, human
  • Phosphoprotein Phosphatases
  • Ppm1d protein, mouse
  • Protein Phosphatase 2C
  • MMP9 protein, human
  • Matrix Metalloproteinase 9