FOXD3 is a tumor suppressor of colon cancer by inhibiting EGFR-Ras-Raf-MEK-ERK signal pathway.
FOXD3 is a tumor suppressor of colon cancer by inhibiting EGFR-Ras-Raf-MEK-ERK signal pathway.
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FOXD3 是一种结肠癌肿瘤抑制因子，通过抑制 EGFR-Ras-Raf-MEK-ERK 信号通路。
DOI：
10.18632/oncotarget.13790
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发表时间：
2017-01-17
期刊：
影响因子：
--
通讯作者：
Li L
中科院分区：
文献类型：
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作者：
Li K;Guo Q;Yang J;Chen H;Hu K;Zhao J;Zheng S;Pang X;Zhou S;Dang Y;Li L
叉头盒D3（FOXD 3）作为一种转录抑制因子，参与发育调控。虽然FoxD 3与几种癌症有关，但其在结肠癌中的作用及其潜在机制仍不清楚。在这里，我们首次发现FOXD 3敲低显著增加了人结肠癌细胞的增殖，增强了细胞侵袭能力并抑制了细胞凋亡。体内异种移植物研究证实，FOXD 3敲低细胞比对照组更具致瘤性。沉默FOXD 3显著激活人结肠癌细胞中的EGFR/Ras/Raf/MEK/ERK通路。此外，阻断EGFR可有效降低FOXD 3敲低诱导的MAPK活性。在人癌组织中，FOXD 3的表达降低，但EGFR/Ras/Raf/MEK/ERK通路被激活。本研究提示FOXD 3可能通过调节EGFR/Ras/Raf/MEK/ERK信号通路对人结肠形成起保护作用。因此，FOXD 3有可能成为结肠癌治疗的新靶点。
Forkhead box D3 (FOXD3), as a transcriptional repressor, is well known to be involved in the regulation of development. Although FoxD3 is associated with several cancers, its role in colon cancer and the underlying mechanism are still unclear. Here, we first showed that FOXD3 knockdown dramatically increased the proliferation of human colon cancer cells, enhanced cell invasive ability and inhibited cell apoptosis. In vivo xenograft studies confirmed that the FOXD3-knockdown cells were more tumorigenic than the controls. Silencing FOXD3 markedly activated EGFR/Ras/Raf/MEK/ERK pathway in human colon cancer cells. In addition, blocking EGFR effectively decreased the activity of MAPK induced by FOXD3 knockdown. In human cancer tissue, the expression of FOXD3 was reduced, however, the EGFR/Ras/Raf/MEK/ERK pathway was activated. Our study indicates that FOXD3 may play a protective role in human colon formation by regulating EGFR/Ras/Raf/MEK/ERK signal pathway. It is proposed that FOXD3 may have potential as a new therapeutic target in human colon cancer treatment.