PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
APE-1/Ref-1 Inhibition Blocks Malignant Pleural Mesothelioma Cell Proliferation and Invasiveness: A Crosstalk between Oxidative Stress and Epithelial Mesenchymal Transition (EMT) in Driving Carcinogenesis and Metastasis
Ramundo, V.; Zanirato, G.; Palazzo, M.L.; Riganti, C.; Aldieri, E. APE-1/Ref-1 Inhibition Blocks Malignant Pleural Mesothelioma Cell Proliferation and Migration: Crosstalk between Oxidative Stress and Epithelial Mesenchymal Transition (EMT) in Driving Carcinogenesis and Metastasis. Int. J. Mol. Sci.2023, 24, 12570.
Ramundo, V.; Zanirato, G.; Palazzo, M.L.; Riganti, C.; Aldieri, E. APE-1/Ref-1 Inhibition Blocks Malignant Pleural Mesothelioma Cell Proliferation and Migration: Crosstalk between Oxidative Stress and Epithelial Mesenchymal Transition (EMT) in Driving Carcinogenesis and Metastasis. Int. J. Mol. Sci. 2023, 24, 12570.
Ramundo, V.; Zanirato, G.; Palazzo, M.L.; Riganti, C.; Aldieri, E. APE-1/Ref-1 Inhibition Blocks Malignant Pleural Mesothelioma Cell Proliferation and Migration: Crosstalk between Oxidative Stress and Epithelial Mesenchymal Transition (EMT) in Driving Carcinogenesis and Metastasis. Int. J. Mol. Sci.2023, 24, 12570.
Ramundo, V.; Zanirato, G.; Palazzo, M.L.; Riganti, C.; Aldieri, E. APE-1/Ref-1 Inhibition Blocks Malignant Pleural Mesothelioma Cell Proliferation and Migration: Crosstalk between Oxidative Stress and Epithelial Mesenchymal Transition (EMT) in Driving Carcinogenesis and Metastasis. Int. J. Mol. Sci. 2023, 24, 12570.
Abstract
Malignant Pleural Mesothelioma (MPM) is an aggressive cancer associated to asbestos exposure. MPM pathogenesis has been related both to oxidative stress, evoked by and in response to asbestos fibers exposure, and the Epithelial Mesenchymal Transition (EMT), an event induced by oxidative stress itself and related to cancer proliferation and metastasis. Asbestos related primary oxidative damage is counteracted in the lung by various redox-sensitive factors, often hyperactivated in some cancers. Among these redox-sensitive factors, Apurinic-apyrimidinic endonuclease 1 (APE-1)/Redox effector factor 1 (Ref-1) has been demonstrated to be overexpressed in MPM and lung cancer, but the molecular mechanism has not yet fully understood. Moreover, asbestos exposure has been associated to induced EMT event, via some EMT transcription factors, such as Twist, Zeb-1 and Snail-1, in a possible crosstalk with oxidative stress and inflammation events. To demonstrate this hypothesis, we inhibited/silenced Ref-1 in MPM cells: as a consequence, both EMT (Twist, Zeb-1 and Snail-1) markers and cellular migration/proliferation were significantly inhibited. Take as a whole, these results show, for the first time, a crosstalk between oxidative stress and EMT in MPM carcinogenesis and invasiveness, so improving the knowledge to better address a preventive and therapeutic approach against this aggressive cancer.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
