Department of Genomic Medicine, GENYO, Centre for Genomics and Oncology, Pfizer-University of Granada and Andalusian Regional Government, PTS, Granada, Spain.
Department of Physiology, Institute of Nutrition and Food Technology "José Mataix Verdú", Biomedical Research Center, University of Granada, Granada, Spain.
Cancer Metastasis Rev. 2023 Mar;42(1):49-85. doi: 10.1007/s10555-022-10077-9. Epub 2023 Jan 26.
Decades of research on oncogene-driven carcinogenesis and gene-expression regulatory networks only started to unveil the complexity of tumour cellular and molecular biology. This knowledge has been successfully implemented in the clinical practice to treat primary tumours. In contrast, much less progress has been made in the development of new therapies against metastasis, which are the main cause of cancer-related deaths. More recently, the role of epigenetic and microenviromental factors has been shown to play a key role in tumour progression. Free radicals are known to communicate the intracellular and extracellular compartments, acting as second messengers and exerting a decisive modulatory effect on tumour cell signalling. Depending on the cellular and molecular context, as well as the intracellular concentration of free radicals and the activation status of the antioxidant system of the cell, the signalling equilibrium can be tilted either towards tumour cell survival and progression or cell death. In this regard, recent advances in tumour cell biology and metastasis indicate that redox signalling is at the base of many cell-intrinsic and microenvironmental mechanisms that control disseminated tumour cell fate and metastasis. In this manuscript, we will review the current knowledge about redox signalling along the different phases of the metastatic cascade, including tumour cell dormancy, making emphasis on metabolism and the establishment of supportive microenvironmental connections, from a redox perspective.
几十年来，关于癌基因驱动的致癌作用和基因表达调控网络的研究，才刚刚开始揭示肿瘤细胞和分子生物学的复杂性。这些知识已成功应用于临床治疗原发性肿瘤。相比之下，针对转移的新疗法的发展进展甚微，而转移是癌症相关死亡的主要原因。最近，表观遗传和微环境因素的作用已被证明在肿瘤进展中发挥关键作用。自由基已知在细胞内和细胞外隔室之间进行通讯，作为第二信使发挥作用，并对肿瘤细胞信号转导产生决定性的调节作用。根据细胞和分子的背景，以及自由基的细胞内浓度和细胞抗氧化系统的激活状态，信号转导平衡可以向肿瘤细胞存活和进展或细胞死亡倾斜。在这方面，肿瘤细胞生物学和转移的最新进展表明，氧化还原信号是控制播散性肿瘤细胞命运和转移的许多内在细胞和微环境机制的基础。在本文中，我们将从氧化还原的角度回顾有关转移级联的不同阶段的氧化还原信号的最新知识，包括肿瘤细胞休眠、强调代谢和建立支持性的微环境联系。
