期刊
EXPERIMENTAL CELL RESEARCH
卷 317, 期 16, 页码 2288-2298出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2011.06.020
关键词
MarvelD3; Tight junctions; Tricellulin; Occludin; EMT; Human pancreatic cancer
资金
- Suhara Memorial Foundation
- Pancreas Research Foundation of Japan
- National Project Knowledge Cluster Initiative
- Ministry of Education, Culture, Sports Science, and Technology
- Ministry of Health, Labour and Welfare of Japan
- Japan Science and Technology Agency
- Program for Developing the Supporting System for Upgrading Education and Research
- Grants-in-Aid for Scientific Research [23590404, 22590336] Funding Source: KAKEN
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.
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