title: Expression of DDX27 contributes to colony-forming ability of gastric cancer cells and correlates with poor prognosis in gastric cancer.
abstract: Previously, we have reported that gain at chromosome 20q13 is the most common genomic copy number aberration in gastric cancer (GC) (29/30 cases), and that among the genes located in this region, we have identified DDX27, whose expression level shows the highest correlation with genomic copy number, as a candidate therapeutic target for GC. Here, we analyzed the clinicopathological significance of DDX27 using immunohistochemistry and studied its functions using knockdown assays. We found that DDX27 was frequently upregulated in GC tissues (98 of 140 cases, 70%), and significantly associated with venous invasion and liver metastasis. Furthermore, multivariate analysis of GC patients showed that high expression of DDX27 was independently associated with poorer prognosis. In functional assays, knockdown of DDX27 reduced the ability of GC cells to form colonies both on conventional plates and soft agar, but had little effect on their invasiveness. We also found that knockdown of DDX27 reduced the viability of GC cells through inhibition of cell cycle progression independently of apoptosis. Interestingly, DDX27 depletion induced accumulation of TP53 in a TP53 wild-type cell line, AGS, but not in a TP53-deleted cell line, 44As3, although DDX27 knockdown commonly reduced the viability of both, indicating the TP53-dependent and independent cell cycle control of DDX27. Thus, our results suggest that expression of DDX27 contributes to colony formation by GC cells through cell cycle control and may be a potential therapeutic target for GC patients with chromosome gain at 20q13.
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University Oita, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tsukamoto
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University Oita, Japan ; Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine, Oita University Oita, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Fumoto
authors.affiliation: Center for Community Medicine, Division of Surgery, Faculty of Medicine, Oita University Oita, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Noguchi
authors.affiliation: Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Chiba, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University Oita, Japan ; Department of Gastroenterology, Faculty of Medicine, Oita University Oita, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hirashita
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University Oita, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Nakada
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University Oita, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hijiya
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University Oita, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University Oita, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsuura
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Oita University Oita, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hamanaka
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Oita University Oita, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Murakami
authors.affiliation: Department of Pathology, Kurume University School of Medicine Fukuoka, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Seto
authors.affiliation: Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine, Oita University Oita, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Inomata
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University Oita, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Moriyama
keywords: 20q13; DDX27; Gastric cancer; RNA helicase; colony formation