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

• Published in: Anticancer research 2014-05, Vol.34 (5), p.2185-2194
• Main Authors: Jia, Shuqin, Jia, Yongning, Weeks, Hoi Ping, Ruge, Fiona, Feng, Xuemin, Ma, Ruiting, Ji, Jiafu, Ren, Jianjun, Jiang, Wen G
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 1791-7530

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). 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. 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. 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.