这篇文章的核心发现是机械力限制，即周围组织施加的物理压力，是触发黑色素瘤细胞从增殖状态转变为侵袭性和耐药性神经元样状态的关键外部因素。研究使用斑马鱼模型和人类黑色素瘤样本，确定了HMGB2这种DNA弯曲蛋白是介导这种表型转换的关键分子，它通过重塑染色质结构来促进侵袭性基因的表达。此外，研究还发现受限细胞会形成乙酰化微管笼以保护细胞核免受机械应力，并且这种侵袭性状态与Notch/BRN2信号通路的上调有关，同时也伴随着细胞增殖的下调和对药物的耐受性。References: Hunter M V, Joshi E, Bowker S, et al. Mechanical confinement governs phenotypic plasticity in melanoma[J]. Nature, 2025: 1-11.
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