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Cell Signal. 2014 Mar;26(3):564-9. doi: 10.1016/j.cellsig.2013.11.030. Epub 2013 Dec 2.

FOXP3 inhibits NF-κB activity and hence COX2 expression in gastric cancer cells.

Author information

1
The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, The Fourth Military Medical University, Xi'an 710032, China.
2
The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: Zhangw90@fmmu.edu.cn.
3
The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: Zhangyqh@fmmu.edu.cn.

Abstract

Gastric cancer remains the main cause of cancer related deaths all over the world, and upregulated COX2 is a key player in its development. The mechanism as to how COX2 is regulated during the gastric cancer development is largely unknown. In this study, we found that the expression of COX2 was closely correlated with NF-κB activity. Strikingly, NF-κB activity was not absolutely consistent with its nuclear localization. Especially, in some cancer cell lines, such as MKN28, there were abundant nuclear localized NF-κB, while NF-κB luciferase activity in this cell line was relatively low. Furthermore, FOXP3 was found to be abundantly expressed in these cells. When the nuclear localized NF-κB expression was adjusted with the expression of FOXP3, it then correlated well with NF-κB activity. Molecularly, increased FOXP3 expression can interact with NF-κB and thus repress its activity. Knockdown of FOXP3 could increase NF-κB activity, COX2 expression, and cell migration. Taken together, our study revealed that function of FOXP3 as a negative regulator of NF-κB activity and thus plays a tumor suppressor role by reducing cell metastasis.

KEYWORDS:

COX2; FOXP3; Gastric cancer; Metastasis; NF-κB

PMID:
24308961
DOI:
10.1016/j.cellsig.2013.11.030
[Indexed for MEDLINE]
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