Wang Mengke, Lyu Hanning, Liu Yuxin, Sun Yang
School of Basic Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, China.
Curr Top Med Chem. 2025 Aug 5. doi: 10.2174/0115680266366687250730060318.
Hepatocellular Carcinoma (HCC) represents a common malignant tumor worldwide, having a profound effect on human health. The processes of invasion and spreading to distant sites are critical malignant biological behaviors exhibited by tumors. The metabolic environment is intricately linked to the initiation, invasion, and subsequent dissemination of tumor cells, with a particular emphasis on lipid metabolism. Lipid metabolism plays a vital role in mediating membrane structure, providing energy, and facilitating signal transduction. It not only delivers energy sources for tumor cells but also establishes conditions conducive to the initiation, progression, and spread of HCC. To meet their energy demands, tumor cells undergo a process of lipid metabolic reprogramming, characterized here as abnormal lipid metabolism. Therefore, a comprehensive investigation into the mechanisms underpinning lipid metabolic reprogramming and its influence on HCC growth and dissemination is crucial for the prevention, early detection, and identification of novel therapeutic targets for HCC. This article initially delineates the metabolic pathways of fatty acids within cells during the development and progression of HCC. It then reviews recent advancements in understanding abnormal lipid metabolism, focusing on the associated genes, enzymes, proteins, and metabolic products that promote HCC progression and spread. Furthermore, a brief overview of the Tumor Immune Microenvironment (TIME) in HCC is provided, highlighting the interactions between Tumor-Associated Macrophages (TAMs) and HCC lipid metabolic reprogramming, as well as their effects on HCC growth and dissemination. Lastly, it examines the treatments targeting abnormal lipid metabolism in HCC utilizing Traditional Chinese Medicine (TCM) and natural products, offering new perspectives for targeting HCC lipid metabolic reprogramming to inhibit spread and invasion.
肝细胞癌（HCC）是全球常见的恶性肿瘤，对人类健康有深远影响。肿瘤的侵袭和远处转移过程是肿瘤表现出的关键恶性生物学行为。代谢环境与肿瘤细胞的起始、侵袭及后续扩散密切相关，尤其强调脂质代谢。脂质代谢在介导膜结构、提供能量和促进信号转导方面发挥着至关重要的作用。它不仅为肿瘤细胞提供能量来源，还为HCC的起始、进展和扩散创造有利条件。为满足能量需求，肿瘤细胞经历脂质代谢重编程过程，在此表现为异常脂质代谢。因此，全面研究脂质代谢重编程的机制及其对HCC生长和扩散的影响，对于HCC的预防、早期检测以及确定新的治疗靶点至关重要。本文首先阐述了HCC发生发展过程中细胞内脂肪酸的代谢途径。然后回顾了对异常脂质代谢理解的最新进展，重点关注促进HCC进展和扩散的相关基因、酶、蛋白质和代谢产物。此外，还简要概述了HCC中的肿瘤免疫微环境（TIME），强调肿瘤相关巨噬细胞（TAMs）与HCC脂质代谢重编程之间的相互作用，以及它们对HCC生长和扩散的影响。最后，研究了利用中药（TCM）和天然产物针对HCC异常脂质代谢的治疗方法，为靶向HCC脂质代谢重编程以抑制扩散和侵袭提供了新的视角。
