Loss of Sprouty2 in human high-grade serous ovarian carcinomas promotes EGF-induced E-cadherin down-regulation and cell invasion

FEBS Lett. 2015 Jan 30;589(3):302-9. doi: 10.1016/j.febslet.2014.12.012. Epub 2014 Dec 20.

Abstract

Sprouty (SPRY) proteins are well-characterized factors that inhibit receptor tyrosine kinase signaling. Our Human Exonic Evidence-Based Oligonucleotide (HEEBO) microarray results showed that the mRNA levels of SPRY2, but not of SPRY1 or SPRY4, are down-regulated in high-grade serous ovarian carcinoma (HGSC) tissues and epithelial ovarian cancer (EOC) cell lines. Molecular inversion probe (MIP) copy number analysis showed the deletion of the SPRY2 locus in HGSC. Overexpression of SPRY2 reduced EGF-induced cell invasion by attenuating EGF-induced E-cadherin down-regulation. Moreover, a positive correlation between SPRY2 and E-cadherin protein levels was observed in HGSC tissues. This study reveals the loss of SPRY2 in HGSC and indicates an important tumor-suppressive role for SPRY2 in mediating the stimulatory effect of EGF on human EOC progression.

Keywords: E-cadherin; Epidermal growth factor; Invasion; Ovarian cancer; Sprouty.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / biosynthesis*
  • Cadherins / genetics
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Membrane Proteins / genetics*
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Signal Transduction / genetics

Substances

  • Cadherins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • SPRY2 protein, human
  • Epidermal Growth Factor