PXD039410-2

PXD039410 is an original dataset announced via ProteomeXchange.

Title	A MYCN-independent mechanism mediating secretome reprogramming and metastasis in MYCN-amplified neuroblastoma
Description	MYCN amplification (MNA) is a defining feature of high-risk neuroblastoma (NB) that predicts poor prognosis. However, whether genes within or in close proximity to the MYCN amplicon also contribute to aggressiveness in MNA+ NB remains poorly understood. Here we identify that GREB1, a transcription factor encoding gene neighboring the MYCN locus, is frequently co-expressed with MYCN, and promotes cell survival in MNA+ NB. GREB1 controls gene expression independently of MYCN in MNA+ NB, among which we uncover Myosin 1B (MYO1B) as being highly expressed in MNA+ NB. MYO1B promotes aggressive features, including invasive capacity in vitro, as well as extravasation and distant metastasis in vivo. Global secretome and proteome profiling further delineate MYO1B as a major regulator of secretome reprogramming in MNA+ NB cells. Moreover, we identify the cytokine MIF as an important pro-invasive and pro-metastatic mediator of MYO1B activity. Together, we have identified a putative GREB1-MYO1B-MIF axis as an unconventional mechanism that promotes the aggressiveness of MNA+ NB, and independently of MYCN. Furthermore, we find that MYO1B is upregulated in association with other oncoproteins during cellular transformation, and is dramatically increased in multiple human cancer types, suggesting a crucial role of MYO1B in cancers in addition to MNA+ NB.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:07:46.417.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christopher Hughes
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; 6x(13)C labeled residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-13 06:45:45	ID requested
1	2023-10-24 11:45:38	announced
⏵ 2	2023-11-14 09:08:53	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:09:14	announced	2024-10-22: Updated project metadata.

Zhang HF, Delaidelli A, Javed S, Turgu B, Morrison T, Hughes CS, Yang X, Pachva M, Lizardo MM, Singh G, Hoffmann J, Huang YZ, Patel K, Shraim R, Kung SHY, Morin GB, Aparicio S, Martinez D, Maris JM, Bosse KR, Williams KC, Sorensen PH, -amplified neuroblastoma. Sci Adv, 9(34):eadg6693(2023) [pubmed]

submitter keyword: MYCN, GREB1, MYO1B,neuroblastoma, secretome

Poul Sorensen
contact affiliation	Senior Scientist, BC Cancer, Vancouver, Canada
contact email	psorensen@bccrc.ca
lab head
Christopher Hughes
contact affiliation	BC Cancer Agency
contact email	chughes@bcgsc.ca
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/2023/10/PXD039410

PRIDE project URI

• PRIDE
  1. PXD039410
     1. Label: PRIDE project
     2. Name: A MYCN-independent mechanism mediating secretome reprogramming and metastasis in MYCN-amplified neuroblastoma