基质硬度能够影响细胞的行为。加州大学的研究人员发现，乳腺组织的硬度与肿瘤转移和患者预后差有关。文章发表在Nature Cell Biology杂志上，文章解析了肿瘤硬度促进癌扩散的分子机制：癌细胞的行为不仅受到生化信号的控制，还会受到生物力学信号的调节。

    为了明确基质硬度对肿瘤行为的具体影响，研究人员使用可以改变硬度的水凝胶对乳腺细胞进行3D培养，以模拟正常乳腺和高硬度的乳腺癌。研究显示，当基质硬度增加时，TWIST1蛋白会介导上皮-间充质细胞转化（EMT）。

    TWIST1原本在细胞质中与G3BP2结合，高硬度基质会促使TWIST1释放出来，移动到细胞核中。TWIST1在那里激活多种基因，帮助乳腺癌细胞入侵周围组织，并转移到机体其他位置。

    研究人员还在小鼠乳腺癌模型中比较了G3BP2缺失造成的影响。研究表明，缺乏G3BP2时肿瘤更具侵袭性，更多地转移到小鼠肺部。

    研究进一步显示，人类乳腺癌中也存在同样的机制。研究人员分析了人类乳腺癌样本，发现肿瘤硬度较高的患者（肿瘤含有更多有组织的胶原结构）生存期比较短。G3BP2水平低而且肿瘤硬度高的患者，生存时间最短。研究人员指出 ，G3BP2蛋白水平和胶原组织形式可以用来预测患者的治疗结果。下一步，我们有希望了解到细胞如何将机械力信号转化为生物学应答。生物力学微环境与肿瘤细胞之间的交流，将为人们提供新的治疗策略，有助于更好的延缓癌症的扩散。

    原文链接：Matrix stiffness drives epithelial–mesenchymal transition and tumour metastasis through a TWIST1–G3BP2 mechanotransduction pathway

    原文摘要：Matrix stiffness potently regulates cellular behaviour in various biological contexts. In breast tumours, the presence of dense clusters of collagen fibrils indicates increased matrix stiffness and correlates with poor survival. It is unclear how mechanical inputs are transduced into transcriptional outputs to drive tumour progression. Here we report that TWIST1 is an essential mechanomediator that promotes epithelial–mesenchymal transition (EMT) in response to increasing matrix stiffness. High matrix stiffness promotes nuclear translocation of TWIST1 by releasing TWIST1 from its cytoplasmic binding partner G3BP2. Loss of G3BP2 leads to constitutive TWIST1 nuclear localization and synergizes with increasing matrix stiffness to induce EMT and promote tumour invasion and metastasis. In human breast tumours, collagen fibre alignment, a marker of increasing matrix stiffness, and reduced expression of G3BP2 together predict poor survival. Our findings reveal a TWIST1–G3BP2 mechanotransduction pathway that responds to biomechanical signals from the tumour microenvironment to drive EMT, invasion and metastasis.