2025-10-17 中国科学院(CAS)
A schematic diagram depicts the metabolic interaction between HCC cells and TAMs (Image by LU Ming’s group)
<関連情報>
- https://english.cas.cn/newsroom/research_news/life/202510/t20251020_1089833.shtml
- https://www.nature.com/articles/s42255-025-01393-9
腫瘍関連マクロファージは、肝細胞癌の転移を促進する酢酸貯蔵庫として機能する Tumour-associated macrophages serve as an acetate reservoir to drive hepatocellular carcinoma metastasis
Li Shen,Shenghao Wang,Chao Gao,Qin Li,Shuya Feng,Weiyan Sun,Xu Liu,Yiyi Ba,Yihui Chu,Yu Zhou,Junjie Pan,Hao Xu,Xu Zhang,Wenwei Zhu,Lunxiu Qin & Ming Lu
Nature Metabolism Published:20 October 2025
DOI:https://doi.org/10.1038/s42255-025-01393-9
Abstract
Increased acetyl-coenzyme A (acetyl-CoA) generation facilitates cancer metastasis and represents a critical metabolic characteristic of metastatic cancers. To maintain high acetyl-CoA levels, cancer cells often enhance the uptake of acetate for acetyl-CoA biosynthesis. However, the microenvironmental source of acetate remains largely unknown. Here we demonstrate that acetate is secreted by tumour-associated macrophages (TAMs) and taken up by hepatocellular carcinoma (HCC) cells to support acetate accumulation. Mechanistically, HCC cell-derived lactate activates the lipid peroxidation–aldehyde dehydrogenase 2 (ALDH2) pathway in TAMs, which promotes the TAMs’ acetate production and secretion. Inhibition of ALDH2 or of lipid peroxidation in TAMs abrogates acetate-induced migration of HCC cells in vitro. In an orthotopic HCC model involving male mice, genetic ablation of ALDH2 in TAMs reduces HCC cell acetate levels and HCC lung metastases. Collectively, our findings reveal a metabolic interaction between HCC cells and TAMs—involving lactate, lipid peroxidation and acetate—and position TAMs as an acetate reservoir that drives HCC metastasis.
