Please use this identifier to cite or link to this item: doi:10.22028/D291-30502
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Title: Redox signals at the ER-mitochondria interface control melanoma progression
Author(s): Zhang, Xin
Gibhardt, Christine S.
Will, Thorsten
Stanisz, Hedwig
Körbel, Christina
Mitkovski, Miso
Stejerean, Ioana
Cappello, Sabrina
Pacheu-Grau, David
Dudek, Jan
Tahbaz, Nasser
Mina, Lucas
Simmen, Thomas
Laschke, Matthias W.
Menger, Michael D.
Schön, Michael P.
Helms, Volkhard
Niemeyer, Barbara A.
Rehling, Peter
Vultur, Adina
Bogeski, Ivan
Language: English
Title: The EMBO journal
Volume: 38
Issue: 15
Startpage: 1
Endpage: 22
Publisher/Platform: EMBO Press
Year of Publication: 2019
Publikation type: Journal Article
Abstract: Reactive oxygen species (ROS) are emerging as important regulators of cancer growth and metastatic spread. However, how cells integrate redox signals to affect cancer progression is not fully understood. Mitochondria are cellular redox hubs, which are highly regulated by interactions with neighboring organelles. Here, we investigated how ROS at the endoplasmic reticulum (ER)-mitochondria interface are generated and translated to affect melanoma outcome. We show that TMX1 and TMX3 oxidoreductases, which promote ER-mitochondria communication, are upregulated in melanoma cells and patient samples. TMX knockdown altered mitochondrial organization, enhanced bioenergetics, and elevated mitochondrial- and NOX4-derived ROS. The TMX-knockdown-induced oxidative stress suppressed melanoma proliferation, migration, and xenograft tumor growth by inhibiting NFAT1. Furthermore, we identified NFAT1-positive and NFAT1-negative melanoma subgroups, wherein NFAT1 expression correlates with melanoma stage and metastatic potential. Integrative bioinformatics revealed that genes coding for mitochondrial- and redox-related proteins are under NFAT1 control and indicated that TMX1, TMX3, and NFAT1 are associated with poor disease outcome. Our study unravels a novel redox-controlled ER-mitochondria-NFAT1 signaling loop that regulates melanoma pathobiology and provides biomarkers indicative of aggressive disease.
DOI of the first publication: 10.15252/embj.2018100871
URL of the first publication:
Link to this record: hdl:20.500.11880/28882
ISSN: 1460-2075
Date of registration: 20-Mar-2020
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Professorship: NT - Prof. Dr. Volkhard Helms
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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