ROS and TGFβ: from pancreatic tumour growth to metastasis

Journal of Experimental & Clinical Cancer Research

Chao-Hui Chang¹  Siim Pauklin¹ 

[1] Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, OX3 7LD, Oxford, UK;

关键词: TGFβ signalling pathway;    Reactive Oxygen Species (ROS);    Epithelial‐to‐mesenchymal transition;    Pancreatic cancer;    Metastasis;    Cancer stem cells (CSCs);   

DOI  :  10.1186/s13046-021-01960-4

来源: Springer

【 摘 要 】

Transforming growth factor β (TGFβ) 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 TGFβ signalling and thereby differentially impact early tumour growth versus metastatic dissemination. TGFβ 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 TGFβ 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.

【 授权许可】

CC BY