title: Association of RAB5 overexpression in pancreatic cancer with cancer progression and poor prognosis via E-cadherin suppression.
abstract: Pancreatic cancer is a common type of cancer with poor prognosis worldwide. Postoperative survival depends on the existence of metastasis. Elucidation of the mechanism underlying cancer progression is important to improve prognosis. The RAS-associated protein RAB5 activates intracellular membrane trafficking, and RAB5 expression is correlated to progression and epithelial mesenchymal transition in various cancers.The expression of RAB5 and E-cadherin in 111 pancreatic cancer samples was investigated by immunohistochemical staining, and the relationship among RAB5 expression, clinicopathological factors, and E-cadherin expression was assessed. Furthermore, RAB5 suppression analysis by siRNA was performed to determine the roles of RAB5 in morphological change, proliferation potency, cell migration ability, and invasiveness of the pancreatic cancer cell line.High RAB5 expression correlated with the presence of lymphatic invasion and venous invasion and low E-cadherin expression. Patients with high RAB5 expression had a poorer prognosis than those with low RAB5 expression. RAB5 suppression in pancreatic cancer cells enhanced E-cadherin expression; changed cell morphology from spindle to round; and inhibited proliferation, invasion, and cell migration.RAB5 contributes to poor prognosis and progression in pancreatic cancer patients. It may be a promising candidate for individualized therapy in refractory pancreatic cancer.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.|Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, Japan.
authors.forename: Takamichi
authors.initials: T
authors.lastname: Igarashi
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.|Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Araki
authors.affiliation: Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research, Maebashi, Gunma, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokobori
authors.affiliation: Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, Japan.
authors.forename: Bolag
authors.initials: B
authors.lastname: Altan
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.|Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamanaka
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.|Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.|Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Tsukagoshi
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.|Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.|Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Kubo
authors.affiliation: Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Handa
authors.affiliation: Department of Surgery and Laparoscopic Surgery, Gunma Prefecture Saiseikai-Maebashi Hospital, Maebashi, Gunma, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hosouchi
authors.affiliation: Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nishiyama
authors.affiliation: Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Oyama
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.|Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.affiliation: Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020696:rab5 GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C427755:RAB5C protein, human; D020696:rab5 GTP-Binding Proteins
keywords: E-cadherin; RAB5; cancer progression; epithelial mesenchymal transition; pancreatic cancer