PXD053068 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | mTORC2-driven chromatin cGAS mediates chemoresistance in colorectal cancer |
Description | Cyclic 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. |
HostingRepository | PRIDE |
AnnounceDate | 2025-05-07 |
AnnouncementXML | Submission_2025-05-06_19:05:16.627.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD053068 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Qian WANG |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-06-13 02:28:36 | ID requested | |
⏵ 1 | 2025-05-06 19:05:17 | announced | |
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 affiliation | Peking university Shenzhen hospital |
contact email | yuan_lin@bjmu.edu.cn |
lab head | |
Qian WANG |
contact affiliation | Shenzhen university |
contact email | wangqianwq1219@163.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD053068
- Label: PRIDE project
- Name: mTORC2-driven chromatin cGAS mediates chemoresistance in colorectal cancer