Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China.
Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin 150086, Heilongjiang Province, China; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 999077, Hong Kong.
Biomed Pharmacother. 2022 Sep;153:113485. doi: 10.1016/j.biopha.2022.113485. Epub 2022 Aug 1.
In multicellular organisms, nutrient uptake and its metabolism are subject to stringent regulation to maintain cellular integrity and prevent aberrant cell proliferation. However, the altered signaling pathways and gene expression disorders in hepatocellular carcinoma (HCC) induce the transformation of metabolic patterns. The reprogrammed metabolic pattern not only conferred HCC cells viability in nutrient-deficient environments, but also contributed to the formation of a unique immune surveillance barrier. Furthermore, in this metabolic pattern, the accumulation of a large number of oxidation products in cells also activates tumor-related signaling pathways. Therefore, the exploration of underlying molecular mechanisms of the metabolic switch will help to improve therapeutic strategies for HCC. We systematically reviewed the landmark events and current research breakthroughs in the study of glucometabolic reprogramming in HCC. Focusing on the central carbon metabolism, the internal energy conversion in HCC and its cancerous mechanisms were fully explained. Furthermore, we also discussed the HCC-specific acellular regulation, metabolic switch of cancer stem cells, oxidative stress adaptation and the formation of immunosuppressive microenvironment, hoping to provide insights for future basic and clinical research.
在多细胞生物中，营养物质的摄取和代谢受到严格的调控，以维持细胞的完整性并防止异常的细胞增殖。然而，肝细胞癌（HCC）中信号通路的改变和基因表达紊乱导致代谢模式的转变。重编程的代谢模式不仅赋予 HCC 细胞在营养缺乏环境中的生存能力，而且有助于形成独特的免疫监视屏障。此外，在这种代谢模式中，细胞内大量氧化产物的积累也会激活肿瘤相关的信号通路。因此，探索代谢开关的潜在分子机制将有助于改善 HCC 的治疗策略。我们系统地回顾了 HCC 中葡萄糖代谢重编程研究的里程碑事件和当前研究突破。重点关注中心碳代谢，充分解释了 HCC 中的内部能量转换及其癌变机制。此外，我们还讨论了 HCC 特有的非细胞调节、肿瘤干细胞的代谢转换、氧化应激适应和免疫抑制微环境的形成，希望为未来的基础和临床研究提供思路。
