Crosstalk between the HIF-1 and Toll-like receptor/nuclear factor-κB pathways in the oral squamous cell carcinoma microenvironment.
Crosstalk between the HIF-1 and Toll-like receptor/nuclear factor-κB pathways in the oral squamous cell carcinoma microenvironment.
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DOI：
10.18632/oncotarget.9329
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发表时间：
2016-06-21
期刊：
影响因子：
--
通讯作者：
Han W
中科院分区：
文献类型：
--
作者：
Han S;Xu W;Wang Z;Qi X;Wang Y;Ni Y;Shen H;Hu Q;Han W
缺氧是实体肿瘤微环境的一个突出特征，可能通过氧敏感转录调控因子缺氧诱导因子-1 （HIF-1）促进肿瘤进展。慢性炎症是另一个典型特征。包括toll样受体（TLRs）和核因子-κB （NF-κB）在内的炎症介质在癌症的发展中起着重要作用。最近的研究揭示了缺氧和炎症信号之间广泛的串扰，尽管机制尚不清楚。我们的研究结果证实了TLR3和TLR4在口腔鳞状细胞癌（OSCC）中高表达。TLR3和TLR4的激活通过NF-κB刺激HIF-1的表达。此外，HIF-1通过直接启动子结合增加TLR3和TLR4的表达。因此，TLR/NF-κB通路与HIF-1形成正反馈回路。这些结果表明，TLR/NF-κB和HIF-1信号之间存在一种新的串扰，这可能有助于OSCC的发生和发展。随着这一新机制的阐明，它可能为未来微环境靶向癌症治疗提供基础。
Hypoxia is a prominent feature of the microenvironment of solid tumors and may contribute to tumor progression through the oxygen-sensitive transcriptional regulator hypoxia-inducible factor-1 (HIF-1). Chronic inflammation is another typical feature. Inflammatory mediators, including Toll-like receptors (TLRs) and nuclear factor-κB (NF-κB), play an important role in cancer development. Recent studies have revealed extensive cross-talk between hypoxia and inflammation signaling, though the mechanisms remain unclear. Our results confirm that TLR3 and TLR4 are highly expressed in oral squamous cell carcinoma (OSCC). Activation of TLR3 and TLR4 stimulated the expression of HIF-1 through NF-κB. In addition, HIF-1 increased the expression of TLR3 and TLR4 through direct promoter binding. Thus, the TLR/NF-κB pathway forms a positive feedback loop with HIF-1. These results indicate a novel cross-talk between the TLR/NF-κB and HIF-1 signaling, which may contribute to OSCC initiation and progression. With the elucidation of this novel mechanism, it might serve as a basis for future microenvironment targeted cancer therapy.
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