PXD028339

PXD028339 is an original dataset announced via ProteomeXchange.

Title	Characterization of proteome-size scaling by integrative omics reveals mechanisms of proliferation control in cancer
Description	Many cell types exhibit remarkable size homogeneity through successive divisions. In both yeast and humans, size homogeneity during division cycles is a result of tight control on the concentration of cell-cycle inhibitors such as WHI5 or RB1 (Retinoblastoma 1) proteins respectively. However, size control is often lost during oncogenesis, correlating with aggression. How size control is affected by mutations which drive proliferation, such as those of the RAS-ERK pathway, or even loss of RB1 itself, is poorly understood. Using quantitative single cell imaging of different melanoma cell lines, we show that melanoma cells exhibit both inter- and intra-line size variability. Integration of imaging with multi-omic data demonstrates that the translation machinery, G2 regulators, inflammatory mediators and growth-regulatory proteins are key determinants of size in melanoma. Theoretical modelling suggests that the cell size of daughter cells is determined by biosynthetic processes and engagement of stress responses in the mother. Biosynthesis and stress in mother cells impacts the synthesis of heritable prodivision factors like Cyclin D1 (CCND1) which control cell progression by inhibiting RB1 in concentration dependent fashions Small cell sizes and uniform populations are driven by robust DNA repair and increased levels of biosynthetic factors which promote CCDN1 accumulation. We propose that increased size and size-heterogeneity in BRAF and NRAS mutated cells is determined by stress or DNA damage in mother’s division cycle that slows cycle progression in the daughters. Such events lead to increased size and senescent-like states. Taken together our data suggest that oncogenic events, such as the dysregulation of MAPK signalling, provide a means to circumvent normal mechanisms of size regulation and increase cell-to-cell variations in size which may drive disease.
HostingRepository	PRIDE
AnnounceDate	2023-01-03
AnnouncementXML	Submission_2023-01-03_03:03:19.307.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JamesWright
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 08:27:11	ID requested
⏵ 1	2023-01-03 03:03:19	announced

Dataset with its publication pending

submitter keyword: Melanoma, MS/MS, Phosphopeptides, TMT, Mouse,Cancer

JyotiChoudhary
contact affiliation	The Institute of Cancer Research
contact email	jyoti.choudhary@icr.ac.uk
lab head
JamesWright
contact affiliation	The Institute of Cancer Research
contact email	james.wright@icr.ac.uk
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/2023/01/PXD028339

PRIDE project URI

• PRIDE
  1. PXD028339
     1. Label: PRIDE project
     2. Name: Characterization of proteome-size scaling by integrative omics reveals mechanisms of proliferation control in cancer