title: Targeting tight junctions during epithelial to mesenchymal transition in human pancreatic cancer.
abstract: Pancreatic cancer continues to be a leading cause of cancer-related death worldwide and there is an urgent need to develop novel diagnostic and therapeutic strategies to reduce the mortality of patients with this disease. In pancreatic cancer, some tight junction proteins, including claudins, are abnormally regulated and therefore are promising molecular targets for diagnosis, prognosis and therapy. Claudin-4 and -18 are overexpressed in human pancreatic cancer and its precursor lesions. Claudin-4 is a high affinity receptor of Clostridium perfringens enterotoxin (CPE). The cytotoxic effects of CPE and monoclonal antibodies against claudin-4 are useful as novel therapeutic tools for pancreatic cancer. Claudin-18 could be a putative marker and therapeutic target with prognostic implications for patients with pancreatic cancer. Claudin-1, -7, tricellulin and marvelD3 are involved in epithelial to mesenchymal transition (EMT) of pancreatic cancer cells and thus might be useful as biomarkers during disease. Protein kinase C is closely related to EMT of pancreatic cancer and regulates tight junctions of normal human pancreatic duct epithelial cells and the cancer cells. This review focuses on the regulation of tight junctions via protein kinase C during EMT in human pancreatic cancer for the purpose of developing new diagnostic and therapeutic modalities for pancreatic cancer.
authors.affiliation: Daisuke Kyuno, Hiroshi Yamaguchi, Tatsuya Ito, Tsuyoshi Kono, Yasutoshi Kimura, Masafumi Imamura, Koichi Hirata, Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kyuno
authors.affiliation: Daisuke Kyuno, Hiroshi Yamaguchi, Tatsuya Ito, Tsuyoshi Kono, Yasutoshi Kimura, Masafumi Imamura, Koichi Hirata, Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Daisuke Kyuno, Hiroshi Yamaguchi, Tatsuya Ito, Tsuyoshi Kono, Yasutoshi Kimura, Masafumi Imamura, Koichi Hirata, Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ito
authors.affiliation: Daisuke Kyuno, Hiroshi Yamaguchi, Tatsuya Ito, Tsuyoshi Kono, Yasutoshi Kimura, Masafumi Imamura, Koichi Hirata, Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kono
authors.affiliation: Daisuke Kyuno, Hiroshi Yamaguchi, Tatsuya Ito, Tsuyoshi Kono, Yasutoshi Kimura, Masafumi Imamura, Koichi Hirata, Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Daisuke Kyuno, Hiroshi Yamaguchi, Tatsuya Ito, Tsuyoshi Kono, Yasutoshi Kimura, Masafumi Imamura, Koichi Hirata, Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Daisuke Kyuno, Hiroshi Yamaguchi, Tatsuya Ito, Tsuyoshi Kono, Yasutoshi Kimura, Masafumi Imamura, Koichi Hirata, Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Konno
authors.affiliation: Daisuke Kyuno, Hiroshi Yamaguchi, Tatsuya Ito, Tsuyoshi Kono, Yasutoshi Kimura, Masafumi Imamura, Koichi Hirata, Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Daisuke Kyuno, Hiroshi Yamaguchi, Tatsuya Ito, Tsuyoshi Kono, Yasutoshi Kimura, Masafumi Imamura, Koichi Hirata, Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
authors.affiliation: Daisuke Kyuno, Hiroshi Yamaguchi, Tatsuya Ito, Tsuyoshi Kono, Yasutoshi Kimura, Masafumi Imamura, Koichi Hirata, Department of Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D057167:Claudins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015195:Drug Design; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D058990:Molecular Targeted Therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D062725:Tight Junction Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D057167:Claudins; D047428:Protein Kinase Inhibitors; D062725:Tight Junction Proteins; D011493:Protein Kinase C
keywords: Claudins; Epithelial to mesenchymal transition; MarvelD3; Normal human pancreatic duct epithelial cells; Pancreatic cancer; Protein kinase C; Tight junctions; Tricellulin