Chiu David Kung-Chun, Zhang Misty Shuo, Tse Aki Pui-Wah, Wong Carmen Chak-Lui
Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong.
Methods Mol Biol. 2019;1928:77-99. doi: 10.1007/978-1-4939-9027-6_6.
Blood vessels in tumors contain chaotic branching structures and leaky vessel lumens, resulting in uneven supply of oxygen in the tumor microenvironment. High metabolic and proliferation rate of tumor cells further depletes the local oxygen supply. Therefore, hypoxia is a common phenomenon in multiple solid malignancies. Hypoxia-inducible factors (HIFs) regulate the transcription of a spectrum of genes, which are vitally important for tumor cell adaption under hypoxia, and shape the tumor microenvironment to become more favorable for progression. HIFs are involved in almost every step of cancer development through inducing angiogenesis, metabolic reprogramming, metastasis, cancer stemness maintenance, chemoresistance, and immune evasion. Here, we describe methods for the assessment of HIF activity, as well as identification of novel transcriptional targets of HIFs in vitro and in vivo.
肿瘤中的血管具有混乱的分支结构和渗漏的血管腔，导致肿瘤微环境中的氧气供应不均。肿瘤细胞的高代谢和增殖率进一步耗尽了局部氧气供应。因此，缺氧是多种实体恶性肿瘤中的常见现象。缺氧诱导因子（HIFs）调节一系列基因的转录，这些基因对于肿瘤细胞在缺氧条件下的适应至关重要，并使肿瘤微环境变得更有利于进展。HIFs通过诱导血管生成、代谢重编程、转移、癌症干性维持、化疗耐药和免疫逃逸，几乎参与了癌症发展的每一个步骤。在这里，我们描述了评估HIF活性的方法，以及在体外和体内鉴定HIF新转录靶点的方法。
