Fig. 2

The proposed cooperation of ROS and TGFβ ligand activation in inducing EMT, invasion and metastasis. Pancreatic acinar cells in adult tissue show high plasticity to under go acinar-to‑ductal metaplasia (ADM), a reversible progress for pancreatic regeneration after injury such as pancreatitis. The progress becomes irreversible upon oncogenic KRAS mutation which leads to pancreatic intraepithelial neoplasia (PanIN) lesions and pancreatic ductal adenocarcinoma (PDAC). Antioxidant expression such as TIGAR is dynamically regulated during the development of pancreatic ductal adenocarcinoma, resulting in lower levels of ROS to promote tumour initiation in the premalignant condition and higher levels of ROS that enable metastatic progression. TGFβ signalling is expected to cooperate with ROS signalling to control EMT, invasion and metastasis in the cancer stem cell (CSC) subpopulation of cells that are particularly metastatic and able to switch their metabolic state due to developmentally plasticity. The PDAC progression from pancreatic acinar cell to metastasis in lung are shown in arrows. The positive and negative interplays between TGFβ, antioxidants and ROS, as well as their positive impacts to cancer progression are shown in arrows and dash inhibitors, respectively