PXD053068

PXD053068 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-13 02:28:36	ID requested
⏵ 1	2025-05-06 19:05:17	announced

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]

submitter keyword: mTORC2,chromatin cGAS, phosphorylation, KGA, chemoresistance

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

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PRIDE project URI

• PRIDE
  1. PXD053068
     1. Label: PRIDE project
     2. Name: mTORC2-driven chromatin cGAS mediates chemoresistance in colorectal cancer