title: Nuclear localization of tricellulin promotes the oncogenic property of pancreatic cancer.
abstract: Accumulating evidence has shown that dysregulation of tight junctions (TJs) is involved in tumor development and progression. In this study, we investigated the expression and subcellular distribution of tricellulin, which constitutes tricellular TJs, using human pancreatic adenocarcinomas. In well-differentiated pancreatic adenocarcinoma tissues, tricellulin immunostaining was prominent in the cytoplasm and the plasma membrane. In contrast, in poorly differentiated tissues, its immunostaining was predominantly observed in the nuclei and was almost absent in the plasma membrane. The distinct immunostaining of tricellulin successfully distinguished poorly differentiated adenocarcinoma from moderately and well-differentiated adenocarcinomas with high levels of sensitivity and specificity. Nuclear tricellulin expression significantly correlated with lymph node metastasis, lymphatic invasion and poor survival. In pancreatic cancer cell lines, tricellulin localization shifted from the membrane to nucleus with decreasing differentiation status. Nuclear localization of tricellulin promoted cell proliferation and invasiveness possibly in association with MAPK and PKC pathways in pancreatic cancers. Our results provide new insights into the function of tricellulin, and its nuclear localization may become a new prognostic factor for pancreatic cancers.
authors.affiliation: Departments of Pathology, Sapporo Medical University School of Medicine, Sapporo 608556, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takasawa
authors.affiliation: Departments of Pathology, Sapporo Medical University School of Medicine, Sapporo 608556, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Murata
authors.affiliation: Departments of Pathology, Sapporo Medical University School of Medicine, Sapporo 608556, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Takasawa
authors.affiliation: Departments of Pathology, Sapporo Medical University School of Medicine, Sapporo 608556, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Departments of Pathology, Sapporo Medical University School of Medicine, Sapporo 608556, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Osanai
authors.affiliation: Departments of Pathology, Sapporo Medical University School of Medicine, Sapporo 608556, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Division of Advanced Medicine Promotion, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nojima
authors.affiliation: Departments of Surgery, Sapporo Medical University School of Medicine, Sapporo 608556, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kono
authors.affiliation: Departments of Surgery, Sapporo Medical University School of Medicine, Sapporo 608556, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Department of Cell Science, Research Institute of Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 608556, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Departments of Pathology, Sapporo Medical University School of Medicine, Sapporo 608556, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
mesh_terms: D021581:Active Transport, Cell Nucleus; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D062794:MARVEL Domain Containing 2 Protein / Q000378:metabolism*; D060787:Neoplasm Grading; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D062794:MARVEL Domain Containing 2 Protein