PXD060607

PXD060607 is an original dataset announced via ProteomeXchange.

Title	Malonyl-CoA Promotes Prostate Cancer Progression and Castration Resistance by Enhancing Lipogenesis and Ran Activation
Description	Malonyl-CoA, as a key metabolite, is not only the building block for lipogenesis, but also a critical metabolic switcher to mediates flux control over mitochondrial FAs β-oxidation in cellular. However, the levels and entire functions of malonyl-CoA in malignancy and drug resistance is still unclear, especially in those characterized by abnormal lipid metabolism, such as prostate cancer (PCa). Here, we showed the levels of malonyl CoA was increased in PCa, especially in castration-resistant prostate cancer (CRPC). Abnormal accumulation of malonyl-CoA promoted lipogenesis and reprogramed multiple metabolism (including lipid, glucose and amino acid metabolism), sustaining cellular homeostasis to contribute to PCa progression. Restoration of MLYCD expression activated PREK-mediated unfolded protein reaction (UPR) via consuming malonyl-CoA. Importantly, we also found that malonyl-CoA as a donor of malonylation, promoted lysine malonylation in PCa. We identified that malonyl-CoA promoted Ran K141 malonylation, increasing Ran activity and enhancing AR nuclear translocation and transcriptional activity, finally contributing to PCa development and resistance to antiandrogens. These findings highlighted the previously unrecognized role and function of MLYCD-mediated malonyl-CoA in PCa progression via the canonical pathway (metabolic reprogramming) and the non-canonical pathway (malonylated Ran K141), systematically revealing that might be a potentially reliable biomarker and therapy for PCa.
HostingRepository	PRIDE
AnnounceDate	2025-08-21
AnnouncementXML	Submission_2025-08-21_06:22:27.072.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yiheng Dai
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	N6-malonyl-L-lysine
Instrument	Orbitrap Astral; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-09 14:42:25	ID requested
⏵ 1	2025-08-21 06:22:27	announced

Dataset with its publication pending

submitter keyword: Human, prostate cell line, 22RV1, LC-MS/MS

Lijie Zhou
contact affiliation	Department of Urology, Henan Institute of Urology and Zhengzhou Key Laboratory for Molecular Biology of Urological Tumor Research, Department Unit of Day Surgery Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
contact email	zhouxiaozhou29@126.com
lab head
Yiheng Dai
contact affiliation	First Affiliated Hospital of Zhengzhou University, Zhengzhou
contact email	978131863@qq.com
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/2025/08/PXD060607

PRIDE project URI

• PRIDE
  1. PXD060607
     1. Label: PRIDE project
     2. Name: Malonyl-CoA Promotes Prostate Cancer Progression and Castration Resistance by Enhancing Lipogenesis and Ran Activation