Please use this identifier to cite or link to this item:Volltext verfügbar? / Dokumentlieferung
|Title:||Redox signals at the ER-mitochondria interface control melanoma progression|
Gibhardt, Christine S.
Laschke, Matthias W.
Menger, Michael D.
Schön, Michael P.
Niemeyer, Barbara A.
|Title:||The EMBO journal|
|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:||https://www.embopress.org/doi/10.15252/embj.2018100871|
|Link to this record:||hdl:20.500.11880/28882|
|Date of registration:||20-Mar-2020|
|Faculty:||NT - Naturwissenschaftlich- Technische Fakultät|
|Department:||NT - Biowissenschaften|
|Professorship:||NT - Prof. Dr. Volkhard Helms|
|Collections:||UniBib – Die Universitätsbibliographie|
Files for this record:
There are no files associated with this item.
Items in SciDok are protected by copyright, with all rights reserved, unless otherwise indicated.