Department of Biology, University of Texas - San Antonio, San Antonio, Texas.
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Endocrinology. 2020 May 1;161(5). doi: 10.1210/endocr/bqaa047.
A hallmark of cancer is the disruption of cellular metabolism during the course of malignant growth. Major focus is now on how these cell-autonomous processes propagate to the tumor microenvironment and, more generally, to the entire host system. This chain of events can have major consequences for a patient's health and wellbeing. For example, metabolic "waste" produced by cancer cells activates systemic inflammatory responses, which can interfere with hepatic insulin receptor signaling and glucose homeostasis. Research is just now beginning to understand how these processes occur, and how they contribute to systemic symptoms prevalent across cancers, including hyperglycemia, fatigue, pain, and sleep disruption. Indeed, it is only recently that we have begun to appreciate that the brain does not play a passive role in responding to cancer-induced changes in physiology. In this review, we provide a brief discussion of how oncogene-directed metabolic reprogramming disrupts host metabolism, with a specific emphasis on cancer-induced hyperglycemia. We further discuss how the brain senses circulating glucose concentrations and how this process goes awry as a response to distant neoplastic growth. Finally, as glucose-sensing neurons control diverse aspects of physiology and behavior, we link cancer-induced changes in energy balance to neuroendocrine and behavioral consequences for the host organism.
癌症的一个标志是恶性生长过程中细胞代谢的紊乱。目前的主要重点是研究这些细胞自主过程如何传播到肿瘤微环境，更普遍地说，传播到整个宿主系统。这一连串的事件可能对患者的健康和福祉产生重大影响。例如，癌细胞产生的代谢“废物”会激活全身炎症反应，从而干扰肝脏胰岛素受体信号和葡萄糖稳态。研究才刚刚开始了解这些过程是如何发生的，以及它们如何导致包括高血糖、疲劳、疼痛和睡眠障碍在内的各种癌症普遍存在的全身症状。事实上，直到最近我们才开始意识到，大脑在应对癌症引起的生理变化时并没有发挥被动作用。在这篇综述中，我们简要讨论了致癌基因定向的代谢重编程如何破坏宿主代谢，特别强调了癌症引起的高血糖。我们进一步讨论了大脑如何感知循环葡萄糖浓度，以及这个过程是如何出错的，作为对远处肿瘤生长的反应。最后，由于葡萄糖感应神经元控制着生理和行为的各个方面，我们将癌症引起的能量平衡变化与宿主生物体的神经内分泌和行为后果联系起来。
