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PXD029132-2

PXD029132 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMitochondrial calcium uniporter controls melanoma aggressive behavior through a redox-controlled phenotype switch
DescriptionMelanoma is the deadliest of skin cancers and has a high tendency to metastasize to distant organs. Calcium and metabolic signals contribute to melanoma invasiveness; however, the underlying molecular details are elusive. The mitochondrial calcium uniporter (MCU) complex is a major route for calcium into the mitochondrial matrix but if and how MCU affects melanoma pathobiology is not understood. Here, we show that MCUA expression correlates with melanoma patient survival, similarly as in kidney, cervical and other cancers, while in pancreatic, breast and liver cancer, this correlation is inverse. Knockdown (KD) of MCUA suppressed melanoma cell growth but promoted migration and invasion in 2D and 3D cultures. In melanoma xenografts, MCUA_KD reduced tumor volumes but promoted lung metastases. Proteomic analyses and protein microarrays identified pathways that link MCUA abundance and melanoma cell phenotype and suggested a major role for metabolic and redox regulation. Accordingly, antioxidants enhanced melanoma cell migration, while pro-oxidants diminished the MCUA_KD-induced invasive phenotype. Furthermore, MCUA_KD amplified the resistance of melanoma cells to immunotherapies and ferroptosis. Col¬lectively, we demonstrate that MCUA controls melanoma aggressive behavior and therapeutic sen¬sitivity. Manipulations of mitochondrial calcium and redox homeostasis, in combination with cur¬rent therapies, should be considered in treating advanced melanoma.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:53:42.353.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChristof Lenz
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentTripleTOF 5600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-10-14 07:59:54ID requested
12022-10-30 08:40:52announced
22023-11-14 08:53:42announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: MCU, cancer,mitochondria, calcium, ROS, redox, invasion, melanoma, phenotype
Contact List
Christof Lenz
contact affiliationCore Facility Proteomics, Department of Clinical Chemistry, University Medical Center Göttingen, Germany
contact emailchristof.lenz@med.uni-goettingen.de
lab head
Christof Lenz
contact affiliationMax Planck Institute for Biophysical Chemistry
contact emailchristof.lenz@mpibpc.mpg.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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