PXD029132-2

PXD029132 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial calcium uniporter controls melanoma aggressive behavior through a redox-controlled phenotype switch
Description	Melanoma 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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:53:42.353.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christof Lenz
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-14 07:59:54	ID requested
1	2022-10-30 08:40:52	announced
⏵ 2	2023-11-14 08:53:42	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: MCU, cancer,mitochondria, calcium, ROS, redox, invasion, melanoma, phenotype

Christof Lenz
contact affiliation	Core Facility Proteomics, Department of Clinical Chemistry, University Medical Center Göttingen, Germany
contact email	christof.lenz@med.uni-goettingen.de
lab head
Christof Lenz
contact affiliation	Max Planck Institute for Biophysical Chemistry
contact email	christof.lenz@mpibpc.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/10/PXD029132

PRIDE project URI

• PRIDE
  1. PXD029132
     1. Label: PRIDE project
     2. Name: Mitochondrial calcium uniporter controls melanoma aggressive behavior through a redox-controlled phenotype switch