TNFα induced FOXP3-NFκB interaction dampens the tumor suppressor role of FOXP3 in gastric cancer cells
TNFα induced FOXP3-NFκB interaction dampens the tumor suppressor role of FOXP3 in gastric cancer cells
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DOI：
10.1016/j.bbrc.2012.11.039
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发表时间：
2013-01-04
影响因子：
3.1
通讯作者：
Zhang, Yingqi
中科院分区：
文献类型：
--
作者：
Hao, Qiang;Li, Weina;Zhang, Yingqi
FOXP3在不同癌症中的作用存在争议，而其在胃癌中的作用在很大程度上是未知的。在这里，我们发现FOXP3在一些胃癌细胞中出乎意料地上调。为了测试增加的FOXP3在胃癌中是否仍然具有在其他癌症中所见的肿瘤抑制作用，我们在基础和TNF α模拟炎症条件下测试其在细胞增殖中的功能。与在基础条件下观察到的增殖抑制作用相比，FOXP3不足以抑制TNF α处理下的细胞增殖。在分子上，我们发现TNF α诱导FOXP3和p65之间的相互作用，这反过来又驱动FOXP3远离众所周知的靶点p21的启动子。我们的数据表明，尽管FOXP 3在胃癌中上调，但由于炎症环境，其肿瘤抑制作用已被削弱。(C)2012 Elsevier Inc. All rights reserved.
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 TNF alpha mimicked inflammatory condition. Compared with the proliferation inhibitory role observed in basal condition, FOXP3 is insufficient to inhibit the cell proliferation under TNF alpha treatment. Molecularly, we found that TNF alpha 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. (C) 2012 Elsevier Inc. All rights reserved.