PXD065649

PXD065649 is an original dataset announced via ProteomeXchange.

Title	Exogenous creatine supplementation promotes tumor metastasis via megakaryocyte creatine kinase B-STAT5B signaling
Description	Creatine supplementation is widely used in sports and increasingly popular among exercising individuals. Although the physiological role of creatine has been extensively studied, the creatine biology in pathological status remains poorly understood. Here we report that exogenous creatine supplementation promotes tumor metastasis via an unexpected platelet activation mechanism in various mouse models and humans. Mechanistically, creatine supplementation increases megakaryocyte creatine concentration and upregulates creatine kinase B (CKB). Unbiased phosphoproteomics reveals that a CKB downstream non-canonical STAT5B phosphorylation instigates various platelet functional genes including purinergic receptor P2Y12 and glycoprotein VI platelet, leading to hyperactive, metastasis-promoting platelets. Megakaryocyte-specific knockout of the creatine transporter Slc6a8 or Stat5b, as well as pharmacological inhibition of STAT5 ablates the creatine-augmented hyperactive platelets and prevents consequent metastasis in mouse models. Importantly, supplement of creatine in healthy volunteers results in hyperactive peripheral platelets that increase metastasis risks. Together, our study sheds novel mechanistic insights into the creatine-induced metastasis risk and provides a new anti-metastatic therapeutic paradigm by targeting megakaryocyte creatine metabolism.
HostingRepository	PRIDE
AnnounceDate	2026-04-27
AnnouncementXML	Submission_2026-04-26_23:48:51.906.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	LIU HUA
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-01 03:01:56	ID requested
⏵ 1	2026-04-26 23:48:52	announced

Dataset with its publication pending

submitter keyword: None

Yunlong Yang
contact affiliation	Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai
contact email	yunlongyang@fudan.edu.cn
lab head
LIU HUA
contact affiliation	Biotree
contact email	support17@biotree.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065649
     1. Label: PRIDE project
     2. Name: Exogenous creatine supplementation promotes tumor metastasis via megakaryocyte creatine kinase B-STAT5B signaling