Downregulation of tight junction-associated MARVEL protein marvelD3 during epithelial-mesenchymal transition in human pancreatic cancer cells

被引：48

作者：

Kojima, Takashi ^{[1
]}

Takasawa, Akira ^{[1
]}

Kyuno, Daisuke ^{[1
,2
]}

Ito, Tatsuya ^{[1
,2
]}

Yamaguchi, Hiroshi ^{[2
]}

Hirata, Koichi ^{[2
]}

Tsujiwaki, Mitsuhiro ^{[1
]}

Murata, Masaki ^{[1
]}

Tanaka, Satoshi ^{[1
]}

Sawada, Norimasa ^{[1
]}

机构：

[1] Sapporo Med Univ, Sch Med, Dept Pathol, Sapporo, Hokkaido 0608556, Japan

[2] Sapporo Med Univ, Sch Med, Dept Surg, Sapporo, Hokkaido 0608556, Japan

来源：

EXPERIMENTAL CELL RESEARCH | 2011年 / 317卷 / 16期

基金：

日本科学技术振兴机构;

关键词：

MarvelD3; Tight junctions; Tricellulin; Occludin; EMT; Human pancreatic cancer; TRANSCRIPTION FACTOR SNAIL; GENE-EXPRESSION; CLAUDIN-1; EXPRESSION; TRICELLULIN; OCCLUDIN; BARRIER; HEPATOCYTES; PATHWAYS; SLUG;

D O I：

10.1016/j.yexcr.2011.06.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-beta 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. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：2288 / 2298

页数：11

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