芳香烃受体
肝细胞癌
癌症研究
烧蚀
转录因子
化学
细胞生物学
生物物理学
生物
医学
内科学
生物化学
基因
作者
Guo-pei Zhang,Zonglin Xie,Juan Jiang,Yutong Zhao,Kai Lei,Zhilong Lin,Shu‐Ling Chen,Tianhong Su,Li Tan,Sui Peng,Ji Wang,Chun Liu,Ming Kuang
标识
DOI:10.1016/j.xcrm.2023.101128
摘要
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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