HIF-1-regulated glucose metabolism a key to apoptosis resistance?
HIF-1-regulated glucose metabolism a key to apoptosis resistance?
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DOI：
10.4161/cc.6.7.4084
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发表时间：
2007-04-01
期刊：
影响因子：
4.3
通讯作者：
Debatin, Klaus-Michael
中科院分区：
文献类型：
--
作者：
Fulda, Simone;Debatin, Klaus-Michael
人类癌症对当前治疗方案的耐药性仍然是肿瘤学的一个挑战。因此，人们对确定导致癌症原发或获得性耐药的分子途径非常感兴趣。缺氧是大多数实体瘤的特征，与治疗反应差有关。在对缺氧的反应中，癌细胞经历各种过继性变化，包括信号通路的激活，从而促进癌细胞存活并阻止细胞死亡。缺氧诱导因子-1 （Hypoxia inducible factor-1, HIF-1）是介导癌细胞适应缺氧环境的主要转录因子。越来越多的证据表明，Hif-1 α， Hif-1的氧敏感亚基，通过上调参与细胞能量代谢的基因，提供防止细胞死亡和刺激肿瘤生长的保护。因此，Hif-1 α和缺氧诱导基因是开发药物抑制剂的有吸引力的靶点，这可能为广泛的成人和儿童恶性肿瘤提供新的治疗选择。
Resistance of human cancers to current treatment regimens remains a challenge in oncology. Therefore, there has been much interest in identifying molecular pathways that are responsible for primary or acquired resistance of cancers. Hypoxia is a characteristic feature of most solid tumors and has been associated with poor treatment response. In response to hypoxia cancer cells undergo a variety of adoptive changes including activation of signaling pathways, which promote cancer cell survival and block cell death. Hypoxia inducible factor-1 (HIF-1) is the major transcription factor that mediates adaptation of cancer cells to the hypoxic environment. There is mounting evidence that Hif-1 alpha, the oxygen sensitive subunit of HIF-1, provides protection against cell death and stimulates tumor growth by upregulating genes that are involved in cellular energy metabolism. Thus, Hif-1 alpha and hypoxia-inducible genes represent attractive targets for the development of pharmacological inhibitors, which may offer new therapeutic options for a wide range of adult and also pediatric malignancies.