TDO2 Promotes the EMT of Hepatocellular Carcinoma Through Kyn-AhR Pathway.
TDO2 Promotes the EMT of Hepatocellular Carcinoma Through Kyn-AhR Pathway.
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TDO2通过Kyn-AhR通路促进肝细胞癌EMT
DOI：
10.3389/fonc.2020.562823
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发表时间：
2020
影响因子：
4.7
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Li L;Wang T;Li S;Chen Z;Wu J;Cao W;Wo Q;Qin X;Xu J
色氨酸2，3-双加氧酶(TDO2)是一种参与色氨酸(Trp)代谢的酶，与多种癌症的一些恶性特征有关。肿瘤细胞中TDO2和吲哚胺2，3-双加氧酶(IDO)催化色氨酸代谢途径的主要产物KYN也被证明激活芳烃受体(AhR)，在一些恶性肿瘤中可能调节肿瘤的生长和侵袭。然而，TDO2是否参与了肝细胞癌的转移和侵袭还未见报道。TDO2在这一过程中的潜在作用机制仍需进一步研究。在这里，我们证明了TDO2的过度表达与肝细胞癌患者的晚期或恶性特征相关。TDO2的敲除或抑制可抑制肝癌细胞在体内外的迁移和侵袭。上皮向间充质转化(EMT)是发生在肿瘤转移初期的重要过程。我们发现，在肝癌细胞中，TDO2促进了EMT过程，EMT生物标志物水平的变化证明了这一点。TDO2通过激活芳香烃受体(AhR)，机械地调节肝癌细胞Kyn的产生。以上结果表明，TDO2通过激活Kyn-AhR通路促进肝细胞癌的EMT，从而参与肝癌的转移和侵袭。
Tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan (Trp) metabolism has been linked with some malignant traits of various cancers. Kyn, the main product of Trp metabolism pathway catalyzed by TDO2 and indoleamine 2,3-dioxygenase (IDO) in tumor cells, was also demonstrated to activate aryl hydrocarbon receptor (AhR), which may regulate cancer growth and invasion in some malignancies. However, whether TDO2 participates in the metastasis and invasion of HCC has not been explored before. The underlying mechanism played by TDO2 in this process still requires further investigation. Here, we demonstrated that overexpression of TDO2 correlates with advanced stage or malignant traits in HCC patients. Knockdown or inhibition of TDO2 suppressed the migration and invasion of HCC cells in vitro and in vivo. Epithelial to mesenchymal transition (EMT) is an essential program happened in the initial phase of cancer metastasis. We found that in HCC cells, TDO2 promoted the EMT process evidenced by altered levels of biomarkers for EMT. Mechanically, TDO2 regulated the Kyn production in HCC cell via activated aryl hydrocarbon receptor (AhR). Together, these results indicate that TDO2 promotes the EMT of hepatocellular carcinoma through activating Kyn-AhR pathway, thereby participating in the metastasis and invasion of HCC.
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影响因子：
81.5
作者：
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通讯作者：
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影响因子：
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