PXD042746

PXD042746 is an original dataset announced via ProteomeXchange.

Title	Integrative omics reveals magnesium deficiency as a driver factor of colorectal cancer
Description	Magnesium (Mg) deficiency is associated with increased risk and malignancy of colorectal cancer (CRC), but the underlying mechanisms remain elusive. In our study, we used genomic, proteomic, and phosphoproteomic data to reveal the effects of low Mg content on genomic instability and tumor metastasis in CRC. Genomic analysis showed that 160 genes co-occurred and had higher mutation frequencies in Low-Mg tumors, including key driver genes such as KMT2C and ERBB3. Unexpectedly, initiation driver genes of CRC, such as TP53 and APC, displayed high mutation frequencies in High-Mg tumors. Additionally, proteomics and phosphoproteomics indicated that the lack of Mg in tumors could activate epithelial-mesenchymal transition (EMT) by modulating inflammation or remodeling the phosphoproteome of cancer cells. Notably, we observed a negative correlation between the level of phosphorylation of DBN1 at S142 (DBN1S142p) and Mg content. Mutation in S142 to D (DBN1S142D) that mimic the effect of phosphorylation upregulated MMP2 and increased cell migration, while MgCl2 treatment reduced DBN1S142p and reversed this phenotype. Mechanistically, our results suggested that Mg2+ weakened the interaction between DBN1 and ACTN4 by reducing DBN1S142p, enhancing the binding of ACTN4 to F-actin and promoting F-actin polymerization, which ultimately reduced MMP2 expression. These findings shed new light on the significance of Mg deficiency in the advancement of CRC and suggest that Mg supplementation could be a promising strategy for prevention and treatment.
HostingRepository	iProX
AnnounceDate	2023-06-05
AnnouncementXML	Submission_2023-06-05_20:33:39.959.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rou Zhang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-05 20:33:17	ID requested
⏵ 1	2023-06-05 20:33:40	announced

Dataset with its publication pending

submitter keyword: Colon cancer, magnesium, omics, genome stability,immunosuppression, metastasis, DBN1

Lunzhi Dai
contact affiliation	Sichuan University
contact email	lunzhi.dai@scu.edu.cn
lab head
Rou Zhang
contact affiliation	Sichuan University
contact email	zhangrou0518@163.com
dataset submitter

iProX dataset URI