2. Academic Validation
  3. A glucose-enriched lung pre-metastatic niche triggered by matrix stiffness-tuned exosomal miRNAs in hepatocellular carcinoma

A glucose-enriched lung pre-metastatic niche triggered by matrix stiffness-tuned exosomal miRNAs in hepatocellular carcinoma

  • Nat Commun. 2025 Feb 18;16(1):1736. doi: 10.1038/s41467-025-56878-8.
Yingying Zhao # 1,  Hongmei Yu # 1,  Jiajun Li # 1,  Jiali Qian 2,  Miao Li 1,  Xi Zhang 1,  Mimi Wang 1,  Yaohui Wang 3,  Yinying Dong 4,  Yang You 5,  Qiwen Zhou 5,  Dongmei Gao 1,  Yan Zhao 1,  Binbin Liu 1,  Rongxin Chen 1,  Zhenggang Ren 1,  Zhiming Wang 6,  Kezhi Zhang 7,  Jiefeng Cui 8
Affiliations

Affiliations

  • 1 Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China.
  • 2 Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai, PR China.
  • 3 Department of Interventional Radiology, Fudan University Shanghai Cancer Center, Shanghai, PR China.
  • 4 Department of Radiation Oncology, The Affiliated Hospital of Qingdao University, Qingdao, PR China.
  • 5 Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, PR China.
  • 6 Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, PR China. wang.zhiming@zs-hospital.sh.cn.
  • 7 Department of Hepatobiliary Surgery, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu Province, PR China. zkz97@njmu.edu.cn.
  • 8 Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, PR China. cui.jiefeng@zs-hospital.sh.cn.
  • # Contributed equally.
PMID: 39966385 DOI: 10.1038/s41467-025-56878-8
Abstract

Apart from the classic features, it is almost unknown whether there exist Other new pathological features during pre-metastatic niche formation in hepatocellular carcinoma (HCC). Our previous works have highlighted the contribution of increased matrix stiffness to lung pre-metastatic niche formation and metastasis in HCC. However, whether increased matrix stiffness influences glucose metabolism and supply of lung pre-metastatic niche remains largely unclear. Here we uncover the underlying mechanism by which matrix stiffness-tuned exosomal miRNAs as the major contributor modulate glucose enrichment during lung pre-metastatic niche formation through decreasing the glucose uptake and consumption of lung fibroblasts and increasing angiogenesis and vascular permeability. Our findings suggest that glucose enrichment, a new characteristic of the lung pre-metastatic niche triggered by matrix stiffness-tuned exosomal miRNAs, is essential for the colonization and survival of metastatic tumor cells, as well as subsequent metastatic foci growth.

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