ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Mechanical Force-Induced cGAS Activation in Carcinoma Cells Facilitates Splenocytes into Liver to Drive Metastasis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Contact percolation governs collective motility via mechano-chemical feedback in heterogeneous breast cancer.Nature communications · 2026Article
- Simulated Microgravity Induced Mesenchymal Stem Cell Senescence via the Activation of Cytosolic mtDNA-cGAS-STING Axis.Journal of cellular physiology · 2026Article
- Splenic B Cells Accumulate and Adopt a Pro-Inflammatory Phenotype to Accelerate Fibrosis in a CClFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Nuclear Mechanotransduction Across the Metastatic Cascade: Decoding Spatiotemporal Heterogeneity in Cancer Dissemination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- Mechanical Force-Induced cGAS Activation in Carcinoma Cells Facilitates Splenocytes into Liver to Drive Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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20 authors.
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Abstract
Liver metastasis is the main cause of cancer-related mortality. During the metastasis process, circulating carcinoma cells hardly pass through narrow capillaries, leading to nuclear deformation. However, the effects of nuclear deformation and its underlying mechanisms on metastasis need further study. Here, it is shown that mechanical force-induced nuclear deformation exacerbates liver metastasis by activating the cGAS-STING pathway, which promotes splenocyte infiltration in the liver. Mechanical force results in nuclear deformation and rupture of the nuclear envelope with inevitable DNA leakage. Cytoplasmic DNA triggers the activation of cGAS-STING pathway, enhancing the production of IL6, TNFα, and CCL2. Additionally, splenocyte recruitment by the proinflammatory cytokines support carcinoma cell survival and colonization in the liver. Importantly, both intervening activity of cGAS and blocking of splenocyte migration to the liver efficiently ameliorate liver metastasis. Overall, these findings reveal a mechanism by which mechanical force-induced nuclear deformation exacerbates liver metastasis by regulating splenocyte infiltration into the liver and support targeting cGAS and blocking splenocyte recruitment as candidate therapeutic approaches for liver metastasis.
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