PXD038081

PXD038081 is an original dataset announced via ProteomeXchange.

Title	Phenotypic heterogeneity analysis of APC-mutant colon cancer by proteomics and phosphoproteomics identifies RAI14 as a key prognostic determinant
Description	Adenomatous polyposis coli (APC) is an important tumor suppressor and most directly related to the regulation of WNT/β-catenin signaling pathway. APC mutation has been identified as an early event in more than 80% of sporadic colorectal cancers (CRCs). However, obvious prognostic differences are observed in CRC patients with APC mutations. Although previous genomics has investigated the roles of concomitant gene mutations in determining the phenotypic heterogeneity of APC-mutant tumors, valuable prognostic determinants for APC-mutant CRC patients are still lacking. By using combined proteome and phosphoproteome, we classified the APC-mutant colon cancer patients and revealed the genomic, proteomic and phosphoproteomic heterogeneity in APC-mutant tumors. Of importance, we identified RAI14 as a key prognostic determinant for APC-mutant colon cancer patients, but not for APC-wildtype colon cancer patients. The heterogeneity and prognostic biomarkers in APC-mutant tumors were further confirmed in Clinical Proteomic Tumor Analysis Consortium (CPTAC) colon cancer cohort. In addition, we found that knockdown of RAI14 in cell lines led to reduced cell migration and changes in some epithelial-mesenchymal transition (EMT)-related markers. Mechanistically, knockdown of RAI14 was able to remodel the phosphoproteome associated with cell adhesion, which might promote F-action degradation and alter the expression of certain EMT markers. Collectively, this work describes the phenotypic heterogeneity of APC-mutant tumors and identifies the prognostic determinants for APC-mutant colon cancer patients. The prognostic utility of RAI14 in APC-mutant colon cancer will provide early warning and increase the chance of successful treatment.
HostingRepository	iProX
AnnounceDate	2022-11-10
AnnouncementXML	Submission_2023-05-06_00:09:44.368.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	2022-11-09 23:05:56	ID requested
1	2022-11-09 23:07:41	announced
⏵ 2	2023-05-06 00:09:46	announced	2023-05-06: Update publication information.

Zhang R, Hu M, Chen HN, Wang X, Xia Z, Liu Y, Wang R, Xia X, Shu Y, Du D, Meng W, Qi S, Li Y, Xu H, Zhou ZG, Dai L, Phenotypic Heterogeneity Analysis of APC-Mutant Colon Cancer by Proteomics and Phosphoproteomics Identifies RAI14 as a Key Prognostic Determinant in East Asians and Westerners. Mol Cell Proteomics, 22(5):100532(2023) [pubmed]

submitter keyword: Colorectal cancer, APC-mutant，RAI14

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