PXD027211

PXD027211 is an original dataset announced via ProteomeXchange.

Title	Primary cilia contribute to the aggressiveness of atypical teratoid/rhabdoid tumors
Description	Atypical teratoid/rhabdoid tumor (AT/RT) is the most common malignant brain tumor in infants and is characterized by loss of nuclear SMARCB1 protein expression. Recent studies show that AT/RTs comprise three molecular subgroups with epigenetic differences, including distinct expression patterns of genes involved in ciliogenesis, but little is known on the functional role of primary cilia in the biology of AT/RT. Here, we show that primary cilia are present across all AT/RT subgroups with specific enrichment in AT/RT-TYR patient samples. Furthermore, we demonstrate that primary ciliogenesis contributes to AT/RT biology in vitro and in vivo. Specifically, we observed a significant decrease in proliferation and clonogenicity following disruption of primary ciliogenesis in AT/RT cell line models. Apoptosis was significantly increased via the induction of STAT1 and DR5 signaling, as detected by proteogenomic profiling. In a Drosophila model of SMARCB1 deficiency, concomitant knockdown of several cilia-associated genes resulted in a substantial shift of the lethal phenotype with more than 20% of flies reaching adulthood. Finally, we demonstrated significantly extended survival in an orthotopic xenograft mouse model of AT/RT upon disruption of primary ciliogenesis, confirming a survival benefit across different species with SMARCB1 deficiency. Altogether, our findings indicate that targeting primary ciliogenesis or its downstream signaling may constitute a novel therapeutic approach for AT/RT.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:34:34.304.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gereon Poschmann
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-09 06:18:39	ID requested
1	2022-10-14 03:29:28	announced
⏵ 2	2023-11-14 07:34:39	announced	2023-11-14: Updated project metadata.

Bl, ü, mel L, Qin N, Berlandi J, Paisana E, Casc, ã, o R, Cust, ó, dia C, Pauck D, Picard D, Langini M, St, ü, hler K, Meyer FD, G, ö, bbels S, Malzkorn B, Liebau MC, Barata JT, Jeibmann A, Kerl K, Erkek S, Kool M, Pfister SM, Johann PD, Fr, ü, hwald MC, Borkhardt A, Reifenberger G, Faria CC, Fischer U, Hasselblatt M, Bartl J, Remke M, Primary cilia contribute to the aggressiveness of atypical teratoid/rhabdoid tumors. Cell Death Dis, 13(9):806(2022) [pubmed]

submitter keyword: Atypical teratoid/rhabdoid tumor, targeted therapy, STAT1/DR5 signaling, primary cilia

Kai Stühler
contact affiliation	Molecular Proteomics Laboratory Institute of Molecular Medicine I Heinrich Heine University Düsseldorf Universitätsstraße 1 40225 Düsseldorf Germany
contact email	kai.stuehler@hhu.de
lab head
Gereon Poschmann
contact affiliation	Molecular Proteomics Laboratory
contact email	gereon.poschmann@hhu.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/PXD027211

PRIDE project URI

• PRIDE
  1. PXD027211
     1. Label: PRIDE project
     2. Name: Primary cilia contribute to the aggressiveness of atypical teratoid/rhabdoid tumors