Narain Radhika, Muncie-Vasic Jonathon M, Weaver Valerie M
Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, California 94143, USA.
Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, Berkeley, California 94720, USA.
Genes Dev. 2025 Jan 7;39(1-2):163-181. doi: 10.1101/gad.352110.124.
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.
发育和疾病是由遗传学与形态发生素、生长因子及细胞因子所刺激的信号通路之间的相互作用来调节的。实验数据凸显了机械力在调节胚胎发育、组织形态发生和恶性肿瘤方面的重要性。力不仅塑造组织运动以驱动胚胎发生和形态发生，还能改变生化信号传导和基因表达的环境以调节细胞和组织命运。不出所料，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传导和基因表达，从而驱动恶性肿瘤和转移，这些改变会增强细胞生长和存活、改变新陈代谢并促进细胞迁移和侵袭。在组织层面，肿瘤相关力会破坏细胞间粘附以扰乱组织结构，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抵抗。现在有了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育的分子机制以及阐明癌症的分子基础至关重要。
