Development and disease are regulated by the interplay between genetics and the signaling pathways stimulated by morphogens, growth factors, and cytokines. Experimental data highlight the importance of mechanical force in regulating embryonic development, tissue morphogenesis, and malignancy. Force not only sculpts tissue movements to drive embryogenesis and morphogenesis but also modifies the context of biochemical signaling and gene expression to regulate cell and tissue fate. Not surprisingly, experiments have demonstrated that perturbations in cell tension drive malignancy and metastasis by altering biochemical signaling and gene expression through modifications in cytoskeletal tension, transmembrane receptor structure and function, and organelle phenotype that enhance cell growth and survival, alter metabolism, and foster cell migration and invasion. At the tissue level, tumor-associated forces disrupt cell–cell adhesions to perturb tissue organization, compromise vascular integrity to induce hypoxia, and interfere with antitumor immunity to foster metastasis and treatment resistance. Exciting new approaches now exist with which to clarify the relationship between mechanotransduction, biochemical signaling, and gene expression in development and disease. Indeed, gaining insight into these interactions is essential to unravel molecular mechanisms that regulate development and clarify the molecular basis of cancer.

中文翻译：

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强制密码：张力调节信号传导以驱动形态发生和恶性肿瘤


发育和疾病受遗传学与形态发生素、生长因子和细胞因子刺激的信号通路之间的相互作用的调节。实验数据强调了机械力在调节胚胎发育、组织形态发生和恶性肿瘤中的重要性。Force 不仅塑造组织运动以驱动胚胎发生和形态发生，而且还改变生化信号传导和基因表达的背景以调节细胞和组织命运。毫不奇怪，实验表明，细胞张力的扰动通过改变细胞骨架张力、跨膜受体结构和功能以及细胞器表型来改变生化信号和基因表达，从而促进细胞生长和存活，改变新陈代谢，促进细胞迁移和侵袭，从而驱动恶性肿瘤和转移。在组织水平上，肿瘤相关力会破坏细胞间粘附以扰乱组织组织，损害血管完整性以诱导缺氧，并干扰抗肿瘤免疫以促进转移和治疗耐药性。现在存在令人兴奋的新方法来阐明发育和疾病中机械转导、生化信号传导和基因表达之间的关系。事实上，深入了解这些相互作用对于揭示调节发展的分子机制和阐明癌症的分子基础至关重要。