Soni Sourabh, Padwad Yogendra S
a Pharmacology and Toxicology Lab, Food and Nutraceuticals Division , CSIR-Institute of Himalayan Bioresource Technology , Palampur , India.
b Academy of Scientific and Innovative Research , New Delhi , India.
Acta Oncol. 2017 Apr;56(4):503-515. doi: 10.1080/0284186X.2017.1301680.
Oxygen (O) homeostasis is an indispensable requirement of eukaryotes. O concentration in cellular milieu is defined as normoxia (∼21% O), physoxia (∼1-13% O) or hypoxia (∼0.1-1% O). Hypoxia, a striking micro-environmental feature in tumorigenesis, is countered by tumor cells via induction of O governed transcription factor, hypoxia inducible factor-1 (HIF-1). Post discovery, HIF-1 has emerged as a promising anticancer therapeutic target during the last two decades. Recent reports have highlighted that enhanced levels of HIF-1 correlate with tumor metastasis leading to poor patient prognosis.
A systematic search in PubMed and SciFinder for the literature on HIF-1 biology and therapeutic importance in cancer was carried out.
This review highlights the initial description as well as the recent insights into HIF-1 biology and regulation. We have focused on emerging data regarding varied classes of HIF-1 target genes affecting various levels of crosstalk among tumorigenic pathways. We have emphasized on the fact that HIF-1 acts as a networking hub coordinating activities of multiple signaling molecules influencing tumorigenesis. Emerging evidences indicate role of many HIF-induced proteomic and genomic alterations in malignant progression by mediating a myriad of genes stimulating angiogenesis, anaerobic metabolism and survival of cancer cells in O-deficient microenvironment.
Better understanding of the crucial role of HIF-1 in carcinogenesis could offer promising new avenues to researchers and aid in elucidating various open issues regarding the use of HIF-1 as an anticancer therapeutic target. In spite of large efforts in this field, many questions still remain unanswered. Hence, future investigations are necessary to devise, assess and refine methods for translating previous research efforts into novel clinical practices in cancer treatment.
氧（O）稳态是真核生物不可或缺的条件。细胞微环境中的氧浓度被定义为常氧（约21% O）、生理性低氧（约1 - 13% O）或低氧（约0.1 - 1% O）。低氧是肿瘤发生过程中一个显著的微环境特征，肿瘤细胞通过诱导氧调控的转录因子缺氧诱导因子-1（HIF-1）来应对。自发现以来，在过去二十年中，HIF-1已成为一个有前景的抗癌治疗靶点。最近的报道强调，HIF-1水平升高与肿瘤转移相关，导致患者预后不良。
在PubMed和SciFinder中系统检索关于HIF-1生物学及其在癌症治疗重要性的文献。
本综述重点介绍了对HIF-1生物学和调控的最初描述以及近期见解。我们关注了关于影响致癌途径中不同水平相互作用的各类HIF-1靶基因的新数据。我们强调了HIF-1作为一个网络枢纽协调多种影响肿瘤发生的信号分子活动这一事实。新出现的证据表明，许多HIF诱导的蛋白质组和基因组改变通过介导众多刺激血管生成、无氧代谢以及癌细胞在缺氧微环境中存活的基因，在恶性进展中发挥作用。
更好地理解HIF-1在致癌过程中的关键作用，可为研究人员提供有前景的新途径，并有助于阐明关于将HIF-1用作抗癌治疗靶点的各种未解决问题。尽管在该领域付出了巨大努力，但许多问题仍未得到解答。因此，未来有必要进行研究，以设计、评估和完善将以往研究成果转化为癌症治疗新临床实践的方法。
