A glucose-enriched lung pre-metastatic niche triggered by matrix stiffness-tuned exosomal miRNAs in hepatocellular carcinoma
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.
Authors
- Zhiming Wang (ORCID: https://orcid.org/0000-0002-7605-377X)
- Rongxin Chen (ORCID: https://orcid.org/0000-0002-3236-5878)
- K. Zhang
- Yan Zhao (ORCID: https://orcid.org/0000-0002-6148-5908)
- Qiwen Zhou (ORCID: https://orcid.org/0000-0002-6598-5643)
- You Yang (ORCID: https://orcid.org/0000-0001-9171-986X)
- Jiefeng Cui (ORCID: https://orcid.org/0000-0001-6996-720X)
- Dongmei Gao (ORCID: https://orcid.org/0000-0003-3442-5704)
- Miao Li (ORCID: https://orcid.org/0000-0001-7840-7511)
- Binbin Liu (ORCID: https://orcid.org/0000-0002-3458-4046)
- Jiajun Li (ORCID: https://orcid.org/0000-0001-6571-0060)
- Yaohui Wang (ORCID: https://orcid.org/0000-0003-0165-6573)
- Yinying Dong (ORCID: https://orcid.org/0009-0007-0660-5093)
- Jiali Qian (ORCID: https://orcid.org/0000-0002-9651-0886)
- Zhenggang Ren (ORCID: https://orcid.org/0000-0002-2799-547X)
- Mimi Wang (ORCID: https://orcid.org/0000-0002-9727-8943)
- Yingying Zhao (ORCID: https://orcid.org/0009-0009-9166-9378)
- Xi Zhang
- Hongmei Yu
Institutions
- Qingdao University (CN)
- Sun Yat-sen University (CN)
- Nantong University (CN)
- Fudan University (CN)
- Fudan University Shanghai Cancer Center (CN)
- Affiliated Hospital of Qingdao University (CN)
- The Affiliated Taizhou People's Hospital of Nanjing Medical University (CN)
- Zhongshan Hospital (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- Ministry of Education (ET)
- Huashan Hospital (CN)
- Taizhou University (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-02-18
- DOI
- https://doi.org/10.1038/s41467-025-56878-8
- Citations
- 22
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 25.33
Funders
- National Natural Science Foundation of China