title: Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in intestinal type gastric cancer.
abstract: Smad interacting protein 1 (SIP1) is an epithelial-mesenchymal transition (EMT)-inducible gene that plays a key role in tumor progression in various cancers. This study seeks to clarify the clinical and biological significance of SIP1 expression, especially in intestinal type gastric cancer. We analyzed the mRNA levels of SIP1 and other EMT regulators by real-time reverse transcription PCR in gastric tissue samples of 134 gastric cancer patients, and in five gastric cancer cell lines. SIP1 gene knockdown by siRNA transfection was performed to evaluate SIP1 function in gastric cancer cells. Expression of the SIP1 gene was significantly higher in cancerous tissue than in adjacent normal mucosa. Although the mRNA expression of the other EMT regulators tested (Snail, Slug, and Twist) was not correlated with clinicopathological factors, increased SIP1 expression was an independent prognostic factor and an independent risk factor for peritoneal dissemination. In addition, SIP1 expression was significantly positive and correlated with vimentin expression. For intestinal type gastric cancer in particular, elevated SIP1 expression was significantly correlated with peritoneal dissemination and poor prognosis (p < 0.05). In vitro, cell proliferation, migration, invasion, and resistance to anoikis were significantly inhibited in SIP1 siRNA-transfected MKN7 cells compared to control siRNA. SIP1 appears to play an important role in progression to peritoneal carcinomatosis and may be a therapeutic target for patients with intestinal type gastric cancer.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. yosinaga@clin.medic.mie-u.ac.jp
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Mikio
authors.initials: M
authors.lastname: Kawamura
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Ohi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Uchida
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mohri
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023102:Anoikis; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D014945:Wound Healing; D055815:Young Adult
chemical_list: C108381:GEMIN2 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins