PXD017658

PXD017658 is an original dataset announced via ProteomeXchange.

Title	MAX-mutant small cell lung cancers exhibit impaired activities of MGA-dependent ncPRC1.6.
Description	The MYC axis is commonly disrupted in cancer, mostly by activation of the MYC family of oncogenes, but also by genetic inactivation of MAX, the obligate partner of MYC, and of the MAX partner, MGA, both of which are members of the polycomb repressive complex, ncPRC1.6. While the oncogenic properties of the MYC family have been extensively studied, the tumor suppressor functions of MAX and MGA and the role of the MYC genes in MAX-mutant cells remain unclear. To address these knowledge gaps, we used chromatin immunoprecipitation, RNA-sequencing and mass spectrometry-based proteomic analysis in MAX-restituted and MYC oncogenic-transformed cell lines derived from human small cell lung cancer (SCLC), which is a high-grade neuroendocrine type of lung cancer. We found that MAX-mutant SCLC cells express ASCL1 and ASCL1-dependent targets, implying that these cells belong to the ASCL1-dependent group of SCLCs. In the absence of MAX, even after ectopic overexpression of MYC, we found no recruitment of MYC to the DNA. Furthermore, MAX reconstitution triggered pro-differentiation expression profiles that shifted when MAX and oncogenic MYC were co-expressed. Although ncPRC1.6 could be formed, the lack of MAX restricted global MGA occupancy, selectively driving its recruitment towards E2F6 motifs. Conversely, MAX restitution enhanced MGA occupancy and global gene repression of genes involved in different functions, including stem-cell and DNA repair/replication. Our data reveal that MAX-mutant SCLCs have ASCL1 characteristics, and are MYC-independent, and that their oncogenic features include deficient ncPRC1.6-mediated gene repression.
HostingRepository	PRIDE
AnnounceDate	2021-09-22
AnnouncementXML	Submission_2021-09-22_06:59:52.101.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joan Josep Bech-Serra
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-20 03:47:08	ID requested
⏵ 1	2021-09-22 06:59:52	announced

Dataset with its publication pending

submitter keyword: cell lung cancer, MAX, proteomics, MAX-gene associated protein, MGA, immunoprecipitation

Montse Sanchez-Cespedes
contact affiliation	Cancer Genetics Group Josep Carreras Leukaemia Research Institute Can Ruti Campus Ctra de Can Ruti, Camí de les Escoles s/n 08916 Badalona, Barcelona Spain
contact email	mscespedes@carrerasresearch.org
lab head
Joan Josep Bech-Serra
contact affiliation	Proteomics Unit - Josep Carreras Leukaemia Research Institute
contact email	jbech@carrerasresearch.org
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/2021/09/PXD017658

PRIDE project URI

• PRIDE
  1. PXD017658
     1. Label: PRIDE project
     2. Name: MAX-mutant small cell lung cancers exhibit impaired activities of MGA-dependent ncPRC1.6.