The relationship between kidney cancer, specifically clear cell renal cell carcinoma (ccRCC), and the hypoxia signaling program has been extensively characterized. Its underlying role as the primary driver of the disease has led to the development of the most effective targeted therapies to date. Cellular responses to hypoxia or mutations affecting the von Hippel-Lindau (VHL) tumor suppressor gene stabilize the hypoxia inducible factor (HIF) transcription factors which then orchestrate elaborate downstream signaling events resulting in adaptations to key biological processes, such as reprogramming metabolism. The direct link of hypoxia signaling to glucose uptake and glycolysis has long been appreciated; however, the HIF family of proteins directly regulate many downstream targets, including other transcription factors with their own extensive networks. In this review, we will summarize our current understanding of how hypoxia signaling regulates other metabolic pathways and how this contributes to the development and progression of clear cell renal cell carcinomas.

肾癌，特别是透明细胞肾细胞癌 (ccRCC) 与缺氧信号传导程序之间的关系已得到广泛表征。它作为疾病主要驱动因素的潜在作用导致了迄今为止最有效的靶向疗法的开发。细胞对缺氧或影响 von Hippel-Lindau (VHL) 肿瘤抑制基因的突变的反应稳定了缺氧诱导因子 (HIF) 转录因子，然后这些转录因子精心策划下游信号事件，从而适应关键的生物过程，例如重编程代谢。缺氧信号与葡萄糖摄取和糖酵解的直接联系早已被人们认识到。然而，HIF 蛋白家族直接调节许多下游靶标，包括具有自己广泛网络的其他转录因子。在这篇综述中，我们将总结目前对缺氧信号如何调节其他代谢途径以及它如何促进透明细胞肾细胞癌的发生和进展的理解。