Spill Fabian, Bakal Chris, Mak Michael
School of Mathematics, University of Birmingham, Birmingham B15 2TT, UK.
Division of Cancer Biology, Chester Beatty Laboratories, The Institute of Cancer Research, London SW3 6JB, UK.
Comput Struct Biotechnol J. 2018 Jul 17;16:237-245. doi: 10.1016/j.csbj.2018.07.002. eCollection 2018.
Mechanics and biochemical signaling are both often deregulated in cancer, leading toincreased cell invasiveness, proliferation, and survival. The dynamics and interactions of cytoskeletal components control basic mechanical properties, such as cell tension, stiffness, and engagement with the extracellular environment, which can lead to extracellular matrix remodeling. Intracellular mechanics can alter signaling and transcription factors, impacting cell decision making. Additionally, signaling from soluble and mechanical factors in the extracellular environment, such as substrate stiffness and ligand density, can modulate cytoskeletal dynamics. Computational models closely integrated with experimental support, incorporating cancer-specific parameters, can provide quantitative assessments and serve as predictive tools toward dissecting the feedback between signaling and mechanics and across multiple scales and domains in tumor progression.
力学和生化信号传导在癌症中常常失调，导致细胞侵袭性、增殖和存活率增加。细胞骨架成分的动力学和相互作用控制着基本的力学特性，如细胞张力、硬度以及与细胞外环境的相互作用，这可能导致细胞外基质重塑。细胞内力学可改变信号传导和转录因子，影响细胞决策。此外，细胞外环境中可溶性和力学因素的信号传导，如底物硬度和配体密度，可调节细胞骨架动力学。与实验支持紧密结合、纳入癌症特异性参数的计算模型，可以提供定量评估，并作为剖析肿瘤进展中信号传导与力学之间以及跨多个尺度和领域的反馈的预测工具。
