FOXP3 inhibits cancer stem cell self-renewal via transcriptional repression of COX2 in colorectal cancer cells.
FOXP3 inhibits cancer stem cell self-renewal via transcriptional repression of COX2 in colorectal cancer cells.
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FOXP3 通过抑制结直肠癌细胞中 COX2 的转录抑制癌症干细胞自我更新
DOI：
10.18632/oncotarget.17974
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发表时间：
2017-07-04
期刊：
影响因子：
--
通讯作者：
Hao Q
中科院分区：
文献类型：
--
作者：
Liu S;Zhang C;Zhang K;Gao Y;Wang Z;Li X;Cheng G;Wang S;Xue X;Li W;Zhang W;Zhang Y;Xing X;Li M;Hao Q
结肠癌干细胞被认为是结肠癌发生和转移的种子细胞。环氧合酶-2（COX 2）是NFκB的下游靶点，在促进肿瘤干细胞更新中起重要作用。然而，C 0X 2在cCSC中如何失调在很大程度上是未知的。在本研究中，我们发现转录因子FOXP 3在球状体中的表达远低于亲本肿瘤细胞。FOXP 3的过表达显著减少了球体的数量，减少了侧群。因此，FOXP 3表达降低了异种移植模型中的肿瘤大小和重量。当另外敲除COX 2时，很少看到FOXP 3的肿瘤抑制作用。FOXP 3通过与COX 2启动子中的NFκB反应元件相互作用，从而抑制p65活性，从而转录抑制COX 2表达。综上所述，我们在此揭示了FOXP 3可能参与通过调节COX 2表达来调节cCSC自我更新，从而为根除结肠癌干细胞提供了新的靶点。
Colon cancer stem cell (cCSC) is considered as the seed cell of colon cancer initiation and metastasis. Cyclooxygenase-2 (COX2), a downstream target of NFκB, is found to be essential in promoting cancer stem cell renewal. However, how COX2 is dysregulated in cCSCs is largely unknown. In this study, we found that the expression of transcription factor FOXP3 was much lower in the spheroids than that in the parental tumor cells. Overexpression of FOXP3 significantly decreased the numbers of spheres, reduced the side population. Accordingly, FOXP3 expression decreased the tumor size and weight in the xenograft model. The tumor inhibitory effects of FOXP3 were rarely seen when COX2 was additionally knocked down. Mechanically, FOXP3 transcriptionally repressed COX2 expression via interacting with and thus inhibiting p65 activity on the putative NFκB response elements in COX2 promoter. Taken together, we here revealed possible involvement of FOXP3 in regulating cCSC self-renewal via tuning COX2 expression, and thus providing a new target for the eradication of colon cancer stem cells.
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影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
9.3
作者：
Annabi B;Laflamme C;Sina A;Lachambre MP;Béliveau R
通讯作者：
Béliveau R
小白菊内酯通过抑制 NF-kappaB/COX-2 通路抑制鼻咽癌细胞的癌干样侧群
影响因子：
12.4
作者：
Liao K;Xia B;Zhuang QY;Hou MJ;Zhang YJ;Luo B;Qiu Y;Gao YF;Li XJ;Chen HF;Ling WH;He CY;Huang YJ;Lin YC;Lin ZN
通讯作者：
Lin ZN
DOI：
10.1016/j.bbrc.2012.11.039
发表时间：
2013-01-04
影响因子：
3.1
作者：
Hao, Qiang;Li, Weina;Zhang, Yingqi
通讯作者：
Zhang, Yingqi
影响因子：
29.4
作者：
Todaro, Matilde;Francipane, Maria Giovanna;Stassi, Giorgio
通讯作者：
Stassi, Giorgio