title: FOXP3 inhibits NF-κB activity and hence COX2 expression in gastric cancer cells.
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.
authors.affiliation: The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hao
authors.affiliation: The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Cun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Shuning
authors.initials: S
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Xue
authors.affiliation: The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D025521:Tumor Suppressor Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: COX2; FOXP3; Gastric cancer; Metastasis; NF-κB