title: Downregulation of tight junction-associated MARVEL protein marvelD3 during epithelial-mesenchymal transition in human pancreatic cancer cells.
abstract: The novel tight junction protein marvelD3 contains a conserved MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain like occludin and tricellulin. However, little is yet known about the detailed role and regulation of marvelD3 in normal epithelial cells and cancer cells, including pancreatic cancer. In the present study, we investigated marvelD3 expression in well and poorly differentiated human pancreatic cancer cell lines and normal pancreatic duct epithelial cells in which the hTERT gene was introduced into human pancreatic duct epithelial cells in primary culture, and the changes of marvelD3 during Snail-induced epithelial-mesenchymal transition (EMT) under hypoxia, TGF-β treatment and knockdown of FOXA2 in well differentiated pancreatic cancer HPAC cells. MarvelD3 was transcriptionally downregulated in poorly differentiated pancreatic cancer cells and during Snail-induced EMT of pancreatic cancer cells in which Snail was highly expressed and the fence function downregulated, whereas it was maintained in well differentiated human pancreatic cancer cells and normal pancreatic duct epithelial cells. Depletion of marvelD3 by siRNAs in HPAC cells resulted in downregulation of barrier functions indicated as a decrease in transepithelial electric resistance and an increase of permeability to fluorescent dextran tracers, whereas it did not affect fence function of tight junctions. In conclusion, marvelD3 is transcriptionally downregulated in Snail-induced EMT during the progression for the pancreatic cancer.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. ktakashi@sapmed.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.forename: Akira
authors.initials: A
authors.lastname: Takasawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kyuno
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tsujiwaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Murata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
mesh_terms: D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D057167:Claudins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics*; D017097:Electric Impedance; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics; D006801:Humans; D062794:MARVEL Domain Containing 2 Protein; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics; D062793:Occludin; D010183:Pancreatic Ducts / Q000166:cytology; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010539:Permeability; D020033:Protein Isoforms / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D000071250:Snail Family Transcription Factors; D013109:Sphingomyelins / Q000378:metabolism; D019098:Telomerase / Q000235:genetics; D019108:Tight Junctions / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D057167:Claudins; C496502:FOXA2 protein, human; C108381:GEMIN2 protein, human; D062794:MARVEL Domain Containing 2 Protein; C516798:MARVELD2 protein, human; C548163:MARVELD3 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C568985:OCLN protein, human; D062793:Occludin; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000071250:Snail Family Transcription Factors; D013109:Sphingomyelins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D051542:Hepatocyte Nuclear Factor 3-beta; C509186:TERT protein, human; D019098:Telomerase