PXD043792

PXD043792 is an original dataset announced via ProteomeXchange.

Title	Oncogenic signals prime cancer cells for toxic cell growth during a G1 cell cycle arrest
Description	A long-term goal in cancer research has been to inhibit the cell cycle in tumour cells without causing toxicity in proliferative healthy tissues. The best evidence that this is achievable is provided by CDK4/6 inhibitors, which arrest the cell cycle in G1, are well-tolerated in patients, and are effective in treating ER+/HER2- breast cancer. CDK4/6 inhibitors are effective because they arrest tumour cells more efficiently than some healthy cell types and, in addition, they affect the tumour microenvironment to enhance anti-tumour immunity. We demonstrate here another reason to explain their efficacy. Tumour cells are specifically vulnerable to CDK4/6 inhibition because during the G1 arrest, oncogenic signals drive toxic cell overgrowth. This overgrowth causes permanent cell cycle withdrawal by either preventing progression from G1 or by inducing replication stress and genotoxic damage during the subsequent S-phase and mitosis. Inhibiting or reverting oncogenic signals that converge onto mTOR can rescue this excessive growth, DNA damage and cell cycle exit in cancer cells. Conversely, inducing oncogenic signals in non-transformed cells can drive these toxic phenotypes and sensitize cells to CDK4/6 inhibition. Together, this demonstrates how oncogenic signals that have evolved to stimulate constitutive tumour growth and proliferation driven subverted to cause toxic cell growth and irreversible cell cycle exit when proliferation is halted in G1.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:14:49.866.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Juan Manuel Valverde
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-14 11:22:31	ID requested
1	2023-11-17 06:13:47	announced
⏵ 2	2024-10-22 06:14:50	announced	2024-10-22: Updated project metadata.

10.1016/J.MOLCEL.2023.10.020;

submitter keyword: oncogenic, G1, cell cycle,Cancer

Adrian Saurin
contact affiliation	Division of Cellular and Systems Medicine, School of Medicine, University of Dundee, UK. DD1 9SY
contact email	a.saurin@dundee.ac.uk
lab head
Juan Manuel Valverde
contact affiliation	University of Dundee
contact email	jvalverde001@dundee.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/2023/11/PXD043792

PRIDE project URI

• PRIDE
  1. PXD043792
     1. Label: PRIDE project
     2. Name: Oncogenic signals prime cancer cells for toxic cell growth during a G1 cell cycle arrest