Tryptophan derivatives regulate the transcription of Oct4 in stem-like cancer cells.
Tryptophan derivatives regulate the transcription of Oct4 in stem-like cancer cells.
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色氨酸衍生物调节干细胞样癌细胞中 Oct4 的转录。
DOI：
10.1038/ncomms8209
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发表时间：
2015-06-10
影响因子：
16.6
通讯作者：
Wang, Ying-Jie
中科院分区：
文献类型：
--
作者：
Cheng, Jie;Li, Wenxin;Kang, Bo;Zhou, Yanwen;Song, Jiasheng;Dan, Songsong;Yang, Ying;Zhang, Xiaoqian;Li, Jingchao;Yin, Shengyong;Cao, Hongcui;Yao, Hangping;Zhu, Chenggang;Yi, Wen;Zhao, Qingwei;Xu, Xiaowei;Zheng, Min;Zheng, Shusen;Li, Lanjuan;Shen, Binghui;Wang, Ying-Jie
芳烃受体（AhR），配体激活的转录因子，响应环境毒物，越来越多地被认为是胚胎发生和肿瘤发生的关键球员。在这里，我们表明，作为内源性AhR配体的各种色氨酸衍生物可以影响主多能性因子Oct4的转录水平。其中，ITE增强AhR与Oct4启动子的结合并抑制其转录。通过色氨酸剥夺或缺氧降低癌细胞中的内源性ITE水平导致Oct4升高，这可以通过施用合成ITE来逆转。因此，合成ITE诱导干细胞样癌细胞的分化，并降低其在皮下和原位异种移植肿瘤模型中的致瘤潜力。因此，我们的研究结果揭示了色氨酸衍生物和AhR信号通路在调节癌细胞干细胞性中的作用，并为靶向干细胞样癌细胞开辟了一条新的治疗途径。 芳烃受体AhR可以调节Oct 4，Oct 4通常在癌症干细胞中表达，并促进多能性和肿瘤发生。在这里，在癌症干细胞中，AhR被色氨酸衍生物ITE激活，这导致Oct4的转录抑制和肿瘤发生减少。
The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that responds to environmental toxicants, is increasingly recognized as a key player in embryogenesis and tumorigenesis. Here we show that a variety of tryptophan derivatives that act as endogenous AhR ligands can affect the transcription level of the master pluripotency factor Oct4. Among them, ITE enhances the binding of the AhR to the promoter of Oct4 and suppresses its transcription. Reduction of endogenous ITE levels in cancer cells by tryptophan deprivation or hypoxia leads to Oct4 elevation, which can be reverted by administration with synthetic ITE. Consequently, synthetic ITE induces the differentiation of stem-like cancer cells and reduces their tumorigenic potential in both subcutaneous and orthotopic xenograft tumour models. Thus, our results reveal a role of tryptophan derivatives and the AhR signalling pathway in regulating cancer cell stemness and open a new therapeutic avenue to target stem-like cancer cells. The aryl hydrocarbon receptor, AhR, can regulate Oct4, which is often expressed in cancer stem cells and promotes pluripotency and tumorigenesis. Here, in cancer stem cells, AhR is shown to be activated by the tryptophan derivative ITE, which causes transcriptional repression of Oct4 and reduced tumorigenesis.
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影响因子：
11.2
作者：
Bunaciu RP;Yen A
通讯作者：
Yen A
影响因子：
16
作者：
Lin, Yuanji;Yang, Ying;Li, Weihua;Chen, Qi;Li, Jie;Pan, Xiao;Zhou, Lina;Liu, Changwei;Chen, Chunsong;He, Jianqin;Cao, Hongcui;Yao, Hangping;Zheng, Li;Xu, Xiaowei;Xia, Zongping;Ren, Jiangtao;Xiao, Lei;Li, Lanjuan;Shen, Binghui;Zhou, Honglin;Wang, Ying-Jie
通讯作者：
Wang, Ying-Jie
影响因子：
1.2
作者：
Ko, Chia-I;Wang, Qin;Fan, Yunxia;Xia, Ying;Puga, Alvaro
通讯作者：
Puga, Alvaro
影响因子：
3.7
作者：
Prud'homme GJ;Glinka Y;Toulina A;Ace O;Subramaniam V;Jothy S
通讯作者：
Jothy S
影响因子：
21.3
作者：
Medema, Jan Paul
通讯作者：
Medema, Jan Paul