Involvement of redox signalling in tumour cell dormancy and metastasis

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.

Automated summary

Decades of research have revealed the complexity of tumour cellular and molecular biology, with some progress made in treating primary tumours. However, less progress has been made in developing therapies against metastasis, which is the main cause of cancer-related deaths. Recent studies have shown that epigenetic and microenvironmental factors play a key role in tumour progression. Free radicals act as second messengers and modulate tumour cell signalling, leading to either cell survival or cell death depending on the context. Redox signalling is involved in controlling disseminated tumour cell fate and metastasis.