Mechanical forces may be generated within a cell due to tissue stiffness, cytoskeletal reorganization, and the changes (even subtle) in the cell's physical surroundings. These changes of forces impose a mechanical tension within the intracellular protein network (both cytosolic and nuclear). Mechanical tension could be released by a series of protein–protein interactions often facilitated by membrane lipids, lectins and sugar molecules and thus generate a type of signal to drive cellular processes, including cell differentiation, polarity, growth, adhesion, movement, and survival. Recent experimental data have accentuated the molecular mechanism of this mechanical signal transduction pathway, dubbed mechanotransduction. Mechanosensitive proteins in the cell's plasma membrane discern the physical forces and channel the information to the cell interior. Cells respond to the message by altering their cytoskeletal arrangement and directly transmitting the signal to the nucleus through the connection of the cytoskeleton and nucleoskeleton before the information despatched to the nucleus by biochemical signaling pathways. Nuclear transmission of the force leads to the activation of chromatin modifiers and modulation of the epigenetic landscape, inducing chromatin reorganization and gene expression regulation; by the time chemical messengers (transcription factors) arrive into the nucleus. While significant research has been done on the role of mechanotransduction in tumor development and cancer progression/metastasis, the mechanistic basis of force-activated carcinogenesis is still enigmatic. Here, in this review, we have discussed the various cues and molecular connections to better comprehend the cellular mechanotransduction pathway, and we also explored the detailed role of some of the multiple players (proteins and macromolecular complexes) involved in mechanotransduction. Thus, we have described an avenue: how mechanical stress directs the epigenetic modifiers to modulate the epigenome of the cells and how aberrant stress leads to the cancer phenotype.

中文翻译：

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染色质的机械转导和表观遗传调节：机械信号在基因调控中的作用

由于组织僵硬、细胞骨架重组以及细胞物理环境的变化（甚至是细微的变化），细胞内可能会产生机械力。这些力的变化在细胞内蛋白质网络（细胞质和细胞核）内施加机械张力。机械张力可以通过一系列通常由膜脂、凝集素和糖分子促进的蛋白质-蛋白质相互作用来释放，从而产生一种信号来驱动细胞过程，包括细胞分化、极性、生长、粘附、运动和生存。最近的实验数据强调了这种机械信号转导途径的分子机制，称为机械转导。细胞质膜中的机械敏感蛋白识别物理力并将信息传递到细胞内部。细胞通过改变细胞骨架的排列来响应信息，并通过细胞骨架和核骨架的连接将信号直接传递到细胞核，然后通过生化信号通路将信息发送到细胞核。力的核传递导致染色质修饰剂的激活和表观遗传景观的调节，诱导染色质重组和基因表达调控；当化学信使（转录因子）到达细胞核时。尽管对于机械转导在肿瘤发展和癌症进展/转移中的作用已经进行了大量研究，但力激活致癌作用的机制基础仍然是个谜。在这篇综述中，我们讨论了各种线索和分子联系，以更好地理解细胞力转导途径，并且我们还探讨了参与力转导的一些多重参与者（蛋白质和大分子复合物）的详细作用。因此，我们描述了一条途径：机械应力如何引导表观遗传修饰剂调节细胞的表观基因组，以及异常应力如何导致癌症表型。