title: TNFα induced FOXP3-NFκB interaction dampens the tumor suppressor role of FOXP3 in gastric cancer cells.
abstract: Controversial roles of FOXP3 in different cancers have been reported previously, while its role in gastric cancer is largely unknown. Here we found that FOXP3 is unexpectedly upregulated in some gastric cancer cells. To test whether increased FOXP3 remains the tumor suppressor role in gastric cancer as seen in other cancers, we test its function in cell proliferation both at basal and TNFα mimicked inflammatory condition. Compared with the proliferation inhibitory role observed in basal condition, FOXP3 is insufficient to inhibit the cell proliferation under TNFα treatment. Molecularly, we found that TNFα induced an interaction between FOXP3 and p65, which in turn drive the FOXP3 away from the promoter of the well known target p21. Our data here suggest that although FOXP3 is upregulated in gastric cancer, its tumor suppressor role has been dampened due to the inflammation environment.
authors.affiliation: The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hao
authors.forename: Weina
authors.initials: W
authors.lastname: Li
authors.forename: Cun
authors.initials: C
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Qin
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Xue
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Shu
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Xu
authors.forename: Yujin
authors.initials: Y
authors.lastname: Xu
authors.forename: Weihua
authors.initials: W
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism*; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins