DNA damage has emerged as a critical factor in fuelling the development and progression of cancer. DNA damage response (DDR) pathways lie at the crux of cell fate decisions following DNA damage induction, which can either trigger the repair of detrimental DNA lesions to protect cancer cells or induce the cell death machinery to eliminate damaged cells. Cytoskeletal dynamics have a critical role to play and influence the proper function of DDR pathways. Microfilaments, intermediate filaments, microtubules, and their associated proteins are well involved in the DDR. For instance, they are not only implicated in the recruitment of specific DDR molecules to the sites of DNA damage but also in the regulation of the mobility of the damaged DNA to repair sites in the periphery of the nucleus. The exquisite roles that these cytoskeletal proteins play in different DDR pathways, such as non-homologous end joining (NHEJ), homologous recombination (HR), base excision repair (BER), and nucleotide excision repair (NER), in cancer cells are extensively discussed in this review. Many cancer treatments are reliant upon inducing DNA damage in cancer cells to eliminate them; thus, it is important to shed light on factors that could affect their efficacy. Although the cytoskeleton is intricately involved in the DDR process, this has often been overlooked in cancer research and has not been exploited in developing DDR-targeting cancer therapy. Understanding the interplay between the cytoskeleton and the DDR in cancer will then provide insights into improving the development of cancer therapies that can leverage the synergistic action of DDR inhibitors and cytoskeleton-targeting agents.
DNA损伤已成为驱动癌症发生发展的关键因素。DNA损伤应答（DDR）通路是DNA损伤诱导后细胞命运决定的核心环节，既可触发有害DNA损伤的修复以保护癌细胞，也能启动细胞死亡机制清除受损细胞。细胞骨架动力学在DDR通路正常功能中发挥着至关重要的调控作用。微丝、中间丝、微管及其相关蛋白深度参与DDR过程：不仅介导特定DDR分子向DNA损伤位点的募集，还调控受损DNA向核周修复区域的定向移动。本综述系统阐述了这些细胞骨架蛋白在癌细胞不同DDR通路（如非同源末端连接、同源重组、碱基切除修复和核苷酸切除修复）中的精妙调控机制。当前多数癌症疗法依赖于诱导癌细胞DNA损伤以实现清除，因此阐明影响疗效的关键因素至关重要。尽管细胞骨架深度参与DDR过程，但这一机制在癌症研究中常被忽视，尚未被充分应用于开发靶向DDR的癌症治疗策略。深入理解癌细胞中细胞骨架与DDR的相互作用机制，将为开发联合应用DDR抑制剂与细胞骨架靶向剂的协同抗癌疗法提供新的理论依据。
Interplay Between the Cytoskeleton and DNA Damage Response in Cancer Progression
肿瘤(癌症)患者之家