ArticleCell reports. Medicine2023
Mechanical confinement promotes heat resistance of hepatocellular carcinoma via SP1/IL4I1/AHR axis.
Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Disrupting fumarylacetoacetate hydrolase by stratified nanoplatforms orchestrates metabolic-immune reprogramming and prevents post-ablation HCC relapse.Nature communications · 2026Article
- IL4I1+ macrophages drive hepatocellular carcinoma progression by responding to biomechanical cues.JHEP reports : innovation in hepatology · 2026Article
- The application of nanoparticle-mediated siRNA delivery systems in ovarian cancer.Cancer gene therapy · 2026Review
- Metabolic characteristics in hepatocellular carcinoma: amino acid metabolic reprogramming.Molecular cancer · 2026Review
- Association of IL4I1Frontiers in immunology · 2026Article
- Nanostrategies synergize with locoregional interventional therapies for boosting antitumor immunity.Bioactive materials · 2025Article
- Article
- Regulating macrophage phenotypes with IL4I1-mimetic nanoparticles in IDD treatment.Journal of nanobiotechnology · 2025Article
- Collagen extracellular matrix promotes gastric cancer immune evasion by activating IL4I1-AHR signaling.Translational oncology · 2024Article
- Mechanisms and therapeutic strategies to combat the recurrence and progression of hepatocellular carcinoma after thermal ablation.Journal of interventional medicine · 2023Article
- IL4I1 in M2-like macrophage promotes glioma progression and is a promising target for immunotherapy.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanical stress can modulate the fate of cells in both physiological and extreme conditions. Recurrence of tumors after thermal ablation, a radical therapy for many cancers, indicates that some tumor cells can endure temperatures far beyond physiological ones. This unusual heat resistance with unknown mechanisms remains a key obstacle to fully realizing the clinical potential of thermal ablation. By developing a 3D bioprinting-based thermal ablation system, we demonstrate that hepatocellular carcinoma (HCC) cells in this 3D model exhibit enhanced heat resistance as compared with cells on plates. Mechanistically, the activation of transcription factor SP1 under mechanical confinement enhances the transcription of Interleukin-4-Induced-1, which catalyzes tryptophan metabolites to activate the aryl hydrocarbon receptor (AHR), leading to heat resistance. Encouragingly, the AHR inhibitor prevents HCC recurrence after thermal ablation. These findings reveal a previously unknown role of mechanical confinement in heat resistance and provide a rationale for AHR inhibitors as neoadjuvant therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.