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PXD053068

PXD053068 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlemTORC2-driven chromatin cGAS mediates chemoresistance in colorectal cancer
DescriptionCyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor that initiates a STING-dependent innate immune response, binds tightly to chromatin, where its catalytic activity is inhibited. However, the mechanisms underlying cGAS recruitment to chromatin and the functions of chromatin-bound cGAS (ccGAS) remain unclear. Here, we demonstrate that mTORC2-mediated serine 37 phosphorylation promotes human cGAS chromatin localization, regulating colorectal cancer cell growth and drug resistance independently of STING. We discovered that ccGAS recruits the SWI/SNF complex at specific chromatin regions to regulate expression of genes involved in glutaminolysis and DNA replication. Knockdown of ccGAS inhibits colorectal cancer cell growth but induces chemoresistance under fluorouracil exposure both in vitro and in vivo. Moreover, inhibition of kidney-type glutaminase (KGA), a downstream target of ccGAS, overcomes chemoresistance induced by ccGAS knockdown in human and murine colorectal cancer. Thus, our study demonstrates that ccGAS coordinates colorectal cancer plasticity and acquired chemoresistance through epigenetic patterning, and illustrates that simultaneously targeting mTORC2-ccGAS and KGA provides a promising theraputic strategy to eliminate quiescent resistant cancer cells.
HostingRepositoryPRIDE
AnnounceDate2025-05-07
AnnouncementXMLSubmission_2025-05-06_19:05:16.627.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD053068
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterQian WANG
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-06-13 02:28:36ID requested
12025-05-06 19:05:17announced
Publication List
10.1038/s41556-024-01473-0;
10.6019/PXD053068;
Lv G, Wang Q, Lin L, Ye Q, Li X, Zhou Q, Kong X, Deng H, You F, Chen H, Wu S, Yuan L, mTORC2-driven chromatin cGAS mediates chemoresistance through epigenetic reprogramming in colorectal cancer. Nat Cell Biol, 26(9):1585-1596(2024) [pubmed]
Keyword List
submitter keyword: mTORC2,chromatin cGAS, phosphorylation, KGA, chemoresistance
Contact List
Lin Yuan
contact affiliationPeking university Shenzhen hospital
contact emailyuan_lin@bjmu.edu.cn
lab head
Qian WANG
contact affiliationShenzhen university
contact emailwangqianwq1219@163.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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