1. NADPH Oxidase NOX4 Is a Critical Mediator of BRAFV600E-Induced Downregulation of the Sodium/Iodide Symporter in Papillary Thyroid Carcinomas
- Author
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Abderrahmane Al Bouzidi, Corinne Dupuy, Jérémy Cailloux, Juliana Cazarin, Jennifer R. Cracchiolo, James A. Fagin, Rabii Ameziane-El-Hassani, Aurore Carré, Martin Schlumberger, Jeffrey A. Knauf, Abir Al Ghuzlan, Mohammed El Mzibri, Naima Azouzi, Dana M. Hartl, Michel Polak, Abdelkarim Filali-Maltouf, Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), LPP - Laboratoire de Phonétique et Phonologie - UMR 7018 (LPP), Université Sorbonne Nouvelle - Paris 3-Centre National de la Recherche Scientifique (CNRS), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biology and Mediacl Research Unit, Centre National de l'Energie, des Sciences et Techniques Nucléaires, Faculté des sciences, Laboratoire de microbiologie et biologie moléculaire, Université Mohammed V de Rabat [Agdal], Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Sodium-iodide symporter ,medicine.medical_specialty ,endocrine system diseases ,Physiology ,Clinical Biochemistry ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biochemistry ,Papillary thyroid cancer ,Thyroid carcinoma ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Internal medicine ,medicine ,Molecular Biology ,ComputingMilieux_MISCELLANEOUS ,General Environmental Science ,NADPH oxidase ,biology ,Chemistry ,Thyroid ,NOX4 ,Cell Biology ,medicine.disease ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Symporter ,biology.protein ,Cancer research ,General Earth and Planetary Sciences - Abstract
Aims: The BRAFV600E oncogene, reported in 40%–60% of papillary thyroid cancer (PTC), has an important role in the pathogenesis of PTC. It is associated with the loss of thyroid iodide-metabolizing genes, such as sodium/iodide symporter (NIS), and therefore with radioiodine refractoriness. Inhibition of mitogen-activated protein kinase (MAPK) pathway, constitutively activated by BRAFV600E, is not always efficient in resistant tumors suggesting that other compensatory mechanisms contribute to a BRAFV600E adaptive resistance. Recent studies pointed to a key role of transforming growth factor β (TGF-β) in BRAFV600E-induced effects. The reactive oxygen species (ROS)-generating NADPH oxidase NOX4, which is increased in PTC, has been identified as a new key effector of TGF-β in cancer, suggestive of a potential role in BRAFV600E-induced thyroid tumors. Results: Here, using two human BRAFV600E-mutated thyroid cell lines and a rat thyroid cell line expressing BRAFV600E in a conditional manner, we show tha...
- Published
- 2017