title: Inhibition of p600 expression suppresses both invasiveness and anoikis resistance of gastric cancer.
abstract: BACKGROUND
  Advanced gastric cancers often metastasize to distant organs and the peritoneum, leading to a poor prognosis. Both invasiveness and resistance to anchorage-independent cell death (anoikis) are important factors in the process of metastasis. p600 (600-kDa protein), recently identified from a cervical cancer cell line, plays a role in both anoikis resistance and cell migration. In this study, we examined whether p600 is involved in the progression of gastric cancer.
  
  
  METHODS
  We used both normal gastric mucosal cells and cancer cells laser-microdissected from 42 gastric cancers and their normal counterparts, and compared their p600 mRNA expression levels with quantitative reverse transcriptase-polymerase chain reaction. We inhibited p600 expression in two gastric cancer cell lines with siRNA and examined its effect on the invasiveness and anoikis resistance both in vitro and in vivo.
  
  
  RESULTS
  Expression of p600 mRNA was significantly higher in gastric cancer cells than in normal mucosal cells (P = 0.027). The invasion assay revealed that invasiveness was significantly reduced by inhibition of p600 (P < 0.01). In vitro experiments revealed that cell viability and colony-formation capacity under anchorage-independent conditions were significantly reduced by inhibition of p600 (P < 0.05). In vivo experiments also showed that the establishment of intraperitoneal disseminated tumors was significantly suppressed by transient inhibition of p600 (P < 0.001).
  
  
  CONCLUSIONS
  Our results strongly suggest that p600 is involved in gastric cancer progression, and has a potential to be a new molecular target for gastric cancer therapy.
authors.affiliation: Department of Surgery and Oncology, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakai
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Lin
authors.initials: L
authors.lastname: Cui
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakata
authors.forename: Hiroki
authors.initials: H
authors.lastname: Toma
authors.forename: Eishi
authors.initials: E
authors.lastname: Nagai
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D023102:Anoikis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007834:Lasers; D051379:Mice; D016513:Mice, SCID; D042282:Microdissection; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering