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Hepatocellular carcinoma (HCC), a highly aggressive cancer with poor prognosis, involves metabolic reprogramming that destabilizes organ homeostasis. HCC cells rewire the hepatic metabolic microenvironment, particularly lipid metabolism, driving dissemination, invasion, and metastasis through a self-reinforcing vicious loop. This review summarizes lipid reprogramming in HCC metastasis and highlights therapeutic strategies targeting lipid metabolism to support more effective systemic therapy.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-switch-triggering-the-invasion-process-lipid-metabolism-in-the-metastasis-of-hepatocellular-carcinoma-review/330877/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-switch-triggering-the-invasion-process-lipid-metabolism-in-the-metastasis-of-hepatocellular-carcinoma-review/330877.png","ImageObject",300,407,{"name":92,"@type":93},"Maeve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does lipid metabolism play in HCC metastasis?","Question",{"text":112,"@type":113},"Lipid metabolism mediates changes in membrane structure, energy supply, and signaling transduction. 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Hepatocellular carcinoma (HCC), which is a highly aggressive disease with a poor prognosis, accounts for most cases of primary liver cancer. As an emerging hallmark of cancers, metabolic reprogramming acts as a runaway mechanism that disrupts homeostasis of the affected organs, including the liver. Specifically, rewiring of the liver metabolic microenvironment, including lipid metabolism, is driven by HCC cells, propelling the phenotypes of HCC cells, including dissemination, invasion, and even metastasis in return. The resulting formation of this vicious loop facilitates various malignant behaviors of HCC further. However, few articles have comprehensively summarized lipid reprogramming in HCC metastasis. Here, we have reviewed the general situation of the liver microenvironment and the physiological lipid metabolism in the liver, and highlighted the effects of different aspects of lipid metabolism on HCC metastasis to explore the underlying mechanisms. In addition, we have recapitulated promising therapeutic strategies targeting lipid metabolism and the effects of lipid metabolic reprogramming on the efficacy of HCC systematical therapy, aiming to offer new perspectives for targeted therapy.  \nKeywords: Hepatocellular carcinoma; Invasion; Metastasis; Lipid metabolism; Tumor microenvironment  \nIntroduction  \nIn China, liver cancer is the second leading cause of cancer-related mortality, illustrating its high malignancy. [1] Moreover, hepatocellular carcinoma (HCC) accounts for more than 80% of primary liver cancer, and is usually characterized by high rates of recurrence as well as metastasis, evolving from chronic liver diseases such as alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), and viral hepatitis. [2] Furthermore, the crosstalk between different components of the liver microenvironment shapes the various functions and dynamic balance of the liver, while also contributes to the occurrence and development of diseases. Due to the shift in the spectrum of HCC and improved understanding of its tumor microenvironment (TME), the metabolic environment has been linked with the oncogenesis, progression, and metastasis in HCC. Specifically, metastasis is one of the most crucial malignant characteristics and most common mortality-related factors of HCC, whose  \n\n| Access this article online |  |\n| --- | --- |\n| Quick Response Code: | Website:\u003Cbr>[www.cmj.org](www.cmj.org) |\n|  | DOI:\u003Cbr>10.1097/CM9.0000000000003144 |\n\nmetabolism characteristic is currently a burgeoning field of study. From formation of an aggressive phenotype to the production of circulating tumor cells (CTCs) and metastatic colonization, the metabolism of glucose, glutamine, and lipids is subjected to dynamic alternation, imparting cancer cells with the ability to metastasize. [3] Notably, lipid metabolism mediates changes in the membrane structure, energy supply, and signaling transduction, fulfilling physiological demands while creating conditions for the occurrence and development of liver cancer, especially metastasis. [4,5]  \nJiaqian Zhang, Zhicheng Zhang, and Zhangfan Wu contributed equally to this work. Correspondence t","cbCainwWjHNLeMlH","https://ap.wps.com/l/cbCainwWjHNLeMlH","pdf",9540414,14,"English","# Abstract\n# Introduction\n## Liver microenvironment, HCC aggressiveness, and metastasis\n## Lipid metabolism in membrane structure, energy, and signaling\n## Therapeutic strategies targeting metabolism\n# Keywords","[{\"question\":\"What role does lipid metabolism play in HCC metastasis?\",\"answer\":\"Lipid metabolism mediates changes in membrane structure, energy supply, and signaling transduction. These shifts help create conditions that support HCC occurrence and progression, especially metastasis.\"},{\"question\":\"Why is metabolic reprogramming considered a key hallmark in cancers such as HCC?\",\"answer\":\"Metabolic reprogramming disrupts homeostasis of affected organs by acting as an uncontrolled mechanism. In HCC, rewiring of the hepatic metabolic microenvironment is driven by cancer cells and promotes malignant behaviors.\"},{\"question\":\"What does the review aim to provide for targeted therapy?\",\"answer\":\"It reviews physiological lipid metabolism in the liver and the effects of lipid metabolism aspects on HCC metastasis. It also recaps promising therapeutic strategies targeting lipid metabolism and the impact of lipid metabolic reprogramming on systemic therapy efficacy.\"}]","The switch triggering the invasion process - Lipid metabolism in the metastasis of hepatocellular carcinoma - Review | PDF",1789990606,35]