Down-regulation of WAVE2, WASP family verprolin-homologous protein 2, in gastric cancer indicates lymph node metastasis and cell migration

Anticancer Res. 2014 May;34(5):2185-94.

Abstract

Background: WAVE2 plays a crucial role in actin polymerisation and cell migration. We aimed to investigate the expression and cellular functions of WAVE2 in human gastric cancer (GC).

Materials and methods: The level of WAVE2 was determined using quantitative PCR (Q-PCR) in a cohort of human gastric tissues. Expression of WAVE2, ARP2, NWASP, ROCK1 and ROCK2 was examined using RT-PCR in paired tissues. WAVE2 and ARP2 protein co-expression was examined. Anti-WAVE2 transgene ribozymes were constructed and transiently transfected into human GC cells.

Results: Down-regulation of WAVE2 expression in GC was significantly correlated with lymph node metastasis. WAVE2 was positively correlated with E-cadherin and negatively with TWIST. Immunohistochemically, WAVE2 and ARP2 were not co-expressed in serial mirror sections. In vitro, WAVE2 knockdown was shown to increase cell motility, whilst ROCK inhibitor treatment reduced this effect in HGC27 cells.

Conclusion: WAVE2 is down-regulated in GC and loses its metastatic role in GC. Knockdown of WAVE2 could increase metastatic potential by promoting the growth, invasiveness, motility, adhesiveness and suppressing EMT (epithelial-mesenchymal transition) of GC cells.

Keywords: ROCK; WAVE2; gastric cancer; lymph node metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Movement* / genetics
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*
  • Transfection
  • Wiskott-Aldrich Syndrome Protein Family / biosynthesis*
  • Young Adult

Substances

  • WASF2 protein, human
  • Wiskott-Aldrich Syndrome Protein Family