Hypoxia promotes migration/invasion and glycolysis in head and neck squamous cell carcinoma via an HIF-1α-MTDH loop
Hypoxia promotes migration/invasion and glycolysis in head and neck squamous cell carcinoma via an HIF-1α-MTDH loop
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缺氧通过 HIF-1α-MTDH 环促进头颈鳞状细胞癌的迁移/侵袭和糖酵解
DOI：
10.3892/or.2017.5949
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发表时间：
2017-11-01
期刊：
影响因子：
4.2
通讯作者：
Liu, Yong
中科院分区：
文献类型：
--
作者：
Zhu, Gangcai;Peng, Fusen;Liu, Yong
缺氧是癌症进展的标志。低氧癌细胞触发糖酵解以响应减少的O-2供应，以满足代谢和生物能量需求。同时，这些对缺氧的反应和微环境的改变通过增加缺氧诱导因子（HIF）调节基因的转录来促进癌细胞转移。然而，缺氧调节癌细胞转移和糖酵解的详细机制仍有待研究。在本研究中，我们发现，metadherin（MTDH），一个多方面的癌基因，参与调节头颈部鳞状细胞癌（HNSCC）的转移和缺氧条件下的侵袭。此外，该研究表明HNSCC细胞中HIF-1 α和MTDH之间存在正反馈回路，并且缺氧通过介导HIF-1 α-MTDH回路促进HNSCC细胞转移和上皮-间质转化。这些发现暗示HIF-1 α-MTDH是实体瘤中抗癌药物的有希望的靶点，并有助于解释我们先前研究中观察到的MTDH对HNSCC的促肿瘤发生和不利影响。
Hypoxia is a hallmark of progressive cancer. Hypoxic cancer cells trigger glycolysis in response to a decreased O-2 supply to meet metabolic and bioenergetic demands. Meanwhile, these responses to hypoxia and alterations of the microenvironment promote cancer cell metastasis by increasing transcription of hypoxia-inducible factor (HIF)-regulated genes. However, the detailed mechanism by which hypoxia regulates cancer cell metastasis and glycolysis remains to be investigated. In the present study, we identified that metadherin (MTDH), a multifaceted oncogene, is involved in the regulation of head and neck squamous cell carcinoma (HNSCC) metastasis and invasion under hypoxic conditions. Furthermore, the study indicated that there is a positive feedback loop between HIF-1 alpha and MTDH in HNSCC cells, and that hypoxia promotes HNSCC cell metastasis and epithelial-mesenchymal transition by mediating the HIF-1 alpha-MTDH loop. These findings implicate HIF-1 alpha-MTDH as a promising target for anticancer drugs in solid tumors, and help to explain the pro-tumorigenic and unfavorable effect of MTDH on HNSCC observed in our previous studies.