文章：

HIF1α和HIF2α：缺氧肿瘤生长和进展中的兄弟姐妹竞争

HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression

原文发布日期：2011-12-15

DOI: 10.1038/nrc3183

类型: Review Article

开放获取: 否

要点：

1. Hypoxia-inducible factor 1α (HIF1α) and HIF2α are broadly expressed in many human cancers, and expression of these proteins frequently correlate with poor patient prognosis.
2. Although HIF1α and HIF2α share some redundant functions, they also exhibit unique and even opposing activities in cell growth, metabolism, angiogenesis, nitric oxide homeostasis and other processes that affect tumour growth.
3. A careful genetic dissection of Hif1a versus Epas1 (which encodes HIF2α) in autochthonous mouse models of cancer is underway, but is only in its infancy. Given that recent results have revealed unanticipated roles for the HIFα subunits in these assays, more work is clearly needed.
4. The HIFs affect many key aspects of tumour initiation, progression, invasion, inflammatory cell recruitment and metastasis; therefore, they represent attractive targets for novel targeted therapies.
5. Surprisingly, HIF1α can function as a tumour suppressor in renal cell carcinoma, whereas HIF2α functions as a tumour suppressor in lung adenocarcinoma. Because HIF inhibitors are being developed for therapeutic benefit, possible tumour-suppressive roles for the HIFs in a minority of human cancers should be carefully assessed.

要点翻译：

1. 缺氧诱导因子1α（HIF1α）与HIF2α在多种人类癌症中广泛表达，且其表达水平常与患者不良预后相关。
2. 尽管HIF1α与HIF2α具有部分重叠功能，但它们在细胞生长、代谢、血管生成、一氧化氮稳态及其他影响肿瘤生长的过程中展现出独特甚至相互拮抗的作用。
3. 目前正在自发性小鼠癌症模型中对Hif1a与Epas1（编码HIF2α基因）进行精细的遗传学解析，但该研究仍处于起步阶段。鉴于近期研究结果揭示了HIFα亚基在这些实验中出人意料的作用，显然需要更深入的研究。
4. HIFs影响肿瘤发生、进展、侵袭、炎症细胞募集及转移等多个关键环节，因此成为新型靶向治疗极具吸引力的作用靶点。
5. 出乎意料的是，在肾细胞癌中HIF1α可发挥肿瘤抑制因子作用，而在肺腺癌中HIF2α则具有肿瘤抑制功能。随着HIF抑制剂正在被开发用于临床治疗，必须审慎评估HIFs在少数人类癌症中可能存在的肿瘤抑制功能。

英文摘要：

Hypoxia-inducible factors (HIFs) are broadly expressed in human cancers, and HIF1α and HIF2α were previously suspected to promote tumour progression through largely overlapping functions. However, this relatively simple model has now been challenged in light of recent data from various approaches that reveal unique and sometimes opposing activities of these HIFα isoforms in both normal physiology and disease. These effects are mediated in part through the regulation of unique target genes, as well as through direct and indirect interactions with important oncoproteins and tumour suppressors, including MYC and p53. As HIF inhibitors are currently undergoing clinical evaluation as cancer therapeutics, a more thorough understanding of the unique roles performed by HIF1α and HIF2α in human neoplasia is warranted.

摘要翻译： 

缺氧诱导因子（HIFs）在人类癌症中广泛表达，HIF1α和HIF2α此前被认为主要通过重叠的功能促进肿瘤进展。然而，这一相对简单的模型现已受到挑战，来自不同方法的最新数据揭示了这两种HIFα亚型在正常生理和疾病中独特且有时相反的作用。这些效应部分通过调控独特的靶基因，以及通过与包括MYC和p53在内的重要癌蛋白和肿瘤抑制因子的直接或间接相互作用介导。由于HIF抑制剂目前正作为癌症治疗药物进行临床评估，因此有必要更深入地了解HIF1α和HIF2α在人类肿瘤发生中所发挥的独特作用。

原文链接：

HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression