PXD053030-1

PXD053030 is an original dataset announced via ProteomeXchange.

Title	Crotonylomics sequencing of human non small cell lung cancer cell lines
Description	Crotonylation is a crotonyl-coenzyme A (CoA)-mediated post-translational modification best known for its roles in epigenetic regulation. Histone lysine crotonylation (Kcr) has been reported to be involved in tumor-related biological functions such as DNA damage repair and immune infiltration. Here we find that abnormal reduction of histone Kcr significantly correlates with a poor response to epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in in-house-established drug-resistant models of lung cancer cell lines, and in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. The crotonyl-CoA-producing enzyme ACSS2 is the key regulator of the resistance-related change of crotonylation. Quantitative crotonylomic, transcriptomic and epigenomic analyses reveal that EGFR-TKI resistance is accompanied by reduced levels of histone 3 lysine 56 crotonylation (H3K56cr) on chromatin, which inhibits transcription of HNF1A and activates the PI3K/AKT signaling pathway. Studies of patient-derived organoids (PDOs) and resistant lung cancer CDX and PDX models treated with a novel histone decrotonylase (HDCR) inhibitor, S67, demonstrate that up-regulation of H3K56cr sensitizes cells to the effect of EGFR-TKIs. These findings uncover the role of histone Kcr in resistance to EGFR-TKIs and suggest a new combination therapy in lung cancer.
HostingRepository	PRIDE
AnnounceDate	2025-09-22
AnnouncementXML	Submission_2025-09-22_02:26:27.546.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	sihong chen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	crotonylated L-lysine
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-11 23:55:45	ID requested
⏵ 1	2025-09-22 02:26:27	announced

10.1073/PNAS.2509255122;

submitter keyword: human;lung cancer;EGFR-TKI resistance;LC-MS

sihong chen
contact affiliation	Shenyang Pharmaceutical University
contact email	chensihong111@163.com
lab head
sihong chen
contact affiliation	Shenyang Pharmaceutical University
contact email	chensihong111@163.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/2025/09/PXD053030

PRIDE project URI

• PRIDE
  1. PXD053030
     1. Label: PRIDE project
     2. Name: Crotonylomics sequencing of human non small cell lung cancer cell lines