FOXP3 promotes tumor growth and metastasis by activating Wnt/β-catenin signaling pathway and EMT in non-small cell lung cancer.
FOXP3 promotes tumor growth and metastasis by activating Wnt/β-catenin signaling pathway and EMT in non-small cell lung cancer.
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FOXP3通过激活Wnt/β-catenin信号通路和EMT促进非小细胞肺癌肿瘤生长和转移
DOI：
10.1186/s12943-017-0700-1
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发表时间：
2017-07-17
期刊：
影响因子：
37.3
通讯作者：
Chen GG
中科院分区：
文献类型：
--
作者：
Yang S;Liu Y;Li MY;Ng CSH;Yang SL;Wang S;Zou C;Dong Y;Du J;Long X;Liu LZ;Wan IYP;Mok T;Underwood MJ;Chen GG
癌细胞FOXP 3在肿瘤发生中的作用是相互矛盾的。本研究旨在探讨FOXP 3在人非小细胞肺癌（NSCLC）中的表达调控、功能及临床意义。本研究招募了106例接受手术的组织学确诊的NSCLC患者。使用肿瘤样品和NSCLC细胞系来检测FOXP 3及其相关分子。进行了与肿瘤发生相关的各种细胞功能。使用体内小鼠肿瘤异种移植物来确认体外结果。FOXP 3高表达的NSCLC患者的总生存率和无复发生存率显著降低。FOXP 3过表达显著诱导细胞增殖、迁移和侵袭，而其抑制则损害其致癌功能。体内研究证实FOXP 3促进肿瘤生长和转移。FOXP 3的异位表达诱导上皮-间质转化（EMT），下调E-钙粘蛋白和上调N-钙粘蛋白，波形蛋白，蜗牛，蛞蝓，和MMP 9。FOXP 3的致癌作用可能归因于FOX 3介导的Wnt/β-catenin信号传导的激活，因为FOXP 3增加了Topflash报告基因的荧光素酶活性，并上调了NSCLC细胞中Wnt信号传导靶基因（包括c-Myc和Cyclin D1）。免疫共沉淀结果进一步表明，FOXP 3可与β-catenin和TCF 4发生物理相互作用，增强β-catenin和TCF 4的功能，诱导Wnt靶基因转录，促进细胞增殖、侵袭和EMT诱导。FOXP 3可作为共激活因子促进Wnt-b-catenin信号通路，诱导EMT和NSCLC中的肿瘤生长和转移。本文的在线版本（doi：10.1186/s12943-017-0700-1）包含补充材料，可供授权用户使用。
The role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC). One hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed. In vivo mouse tumor xenograft was used to confirm the in vitro results. NSCLC patients with the high level of FOXP3 had a significant decrease in overall survival and recurrence-free survival. FOXP3 overexpression significantly induced cell proliferation, migration, and invasion, whereas its inhibition impaired its oncogenic function. In vivo studies confirmed that FOXP3 promoted tumor growth and metastasis. The ectopic expression of FOXP3 induced epithelial–mesenchymal transition (EMT) with downregulation of E-cadherin and upregulation of N-cadherin, vimentin, snail, slug, and MMP9. The oncogenic effects by FOXP3 could be attributed to FOX3-mediated activation of Wnt/β-catenin signaling, as FOXP3 increased luciferase activity of Topflash reporter and upregulated Wnt signaling target genes including c-Myc and Cyclin D1 in NSCLC cells. Co-immunoprecipitation results further indicated that FOXP3 could physically interacted with β-catenin and TCF4 to enhance the functions of β-catenin and TCF4, inducing transcription of Wnt target genes to promote cell proliferation, invasion and EMT induction. FOXP3 can act as a co-activator to facilitate the Wnt-b-catenin signaling pathway, inducing EMT and tumor growth and metastasis in NSCLC. The online version of this article (doi:10.1186/s12943-017-0700-1) contains supplementary material, which is available to authorized users.
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影响因子：
11.2
作者：
Li W;Wang L;Katoh H;Liu R;Zheng P;Liu Y
通讯作者：
Liu Y
影响因子：
11.2
作者：
Liu R;Yi B;Wei S;Yang WH;Hart KM;Chauhan P;Zhang W;Mao X;Liu X;Liu CG;Wang L
通讯作者：
Wang L
影响因子：
5.3
作者：
Tao, Hiroyuki;Mimura, Yusuke;Ueoka, Hiroshi
通讯作者：
Ueoka, Hiroshi
影响因子：
11.2
作者：
Hinz, Sebastian;Pagerols-Raluy, Laia;Kalthoff, Holger
通讯作者：
Kalthoff, Holger
EMT，癌症干细胞和耐药性：癌症战争中新兴的邪恶轴。
影响因子：
8
作者：
Singh, A.;Settleman, J.
通讯作者：
Settleman, J.