ROS and TGFβ: from pancreatic tumour growth to metastasis

Transforming growth factor beta (TGF beta) signalling pathway switches between anti-tumorigenic function at early stages of cancer formation and pro-tumorigenic effects at later stages promoting cancer metastasis. A similar contrasting role has been uncovered for reactive oxygen species (ROS) in pancreatic tumorigenesis. Down-regulation of ROS favours premalignant tumour development, while increasing ROS level in pancreatic ductal adenocarcinoma (PDAC) enhances metastasis. Given the functional resemblance, we propose that ROS-mediated processes converge with the spatial and temporal activation of TGF beta signalling and thereby differentially impact early tumour growth versus metastatic dissemination. TGF beta signalling and ROS could extensively orchestrate cellular processes and this concerted function can be utilized by cancer cells to facilitate their malignancy. In this article, we revisit the interplay of canonical and non-canonical TGF beta signalling with ROS throughout pancreatic tumorigenesis and metastasis. We also discuss recent insight that helps to understand their conflicting effects on different stages of tumour development. These considerations open new strategies in cancer therapeutics.

Automated summary

The TGF beta signaling pathway and ROS have contrasting effects on early tumorigenesis and metastasis in pancreatic cancer, suggesting a potential synergistic role in promoting cancer malignancy.