PXD008220

PXD008220 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteome analysis of DLC1 in breast cancer
Description	Deleted in Liver Cancer-1 (DLC1), a member of the RhoGAP family of proteins, functions as a tumor suppressor in several cancers including breast cancer. However, its clinical relevance is unclear in breast cancer. In this study, expression of DLC1 was correlated with prognosis using publicly available breast cancer gene expression datasets and quantitative Reverse Transcription PCR in cohorts of Estrogen Receptor-positive (ER+) breast cancer. Mutation and methylation status of DLC1 were assessed in these datasets including The Cancer Genome Atlas (TCGA). To seek further insights in understanding the role of DLC1 in ER+ breast cancer, we developed a knock-in model of DLC1 in T47D breast cancer cells. Label-free global proteomic and TiO2 phosphopeptide enrichment assays were performed and validated using Western blotting. Here, we report that low expression of DLC1 correlates with poor prognosis in patients with ER+ breast cancer with further decrease in metastatic lesions. Analysis of the TCGA data showed that down regulation of DLC1 is not due to methylation or mutations. Stable knock-in of DLC1-full-length inhibits cell growth significantly in vitro compared to its control counterpart. 6726 phosphopeptides were quantified by phosphoproteomics analysis in both conditons, whereas 205 and 122 were unique to DLC1 knock-in and T47D-control cells, respectively. Pathway analysis using DAVID showed the top three significant clusters of differentially identified phosphopeptides involving cell-cell adhesion, mRNA processing and splicing, and transcription regulation. Decreased phosphorylation of epithelial cell transforming sequence 2 (ECT2) at the residue T359, critical for its active conformational change was validated. In conclusion, this data suggests that high expression of DLC1 reduces cell growth and is associated with favorable prognosis. Our results document an inverse relation between ECT2 phosphorylation and DLC1 expression, promising a novel strategy for treating ER+ breast cancer.
HostingRepository	PRIDE
AnnounceDate	2018-10-04
AnnouncementXML	Submission_2018-10-04_09:44:25.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD008220
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jason True
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Phospho; Oxidation; Carbamidomethyl
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-11-15 08:04:33	ID requested
⏵ 1	2018-10-04 09:44:26	announced

G, ö, kmen-Polar Y, True JD, Vieth E, Gu Y, Gu X, Qi GD, Mosley AL, Badve SS, Quantitative phosphoproteomic analysis identifies novel functional pathways of tumor suppressor DLC1 in estrogen receptor positive breast cancer. PLoS One, 13(10):e0204658(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: Breast cancer, DLC1, phosphoproteome

Sunil Badve
contact affiliation	Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN
contact email	sbadve@iupui.edu
lab head
Jason True
contact affiliation	Indiana University School of Medicine
contact email	jdtrue@iu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008220
     1. Label: PRIDE project
     2. Name: Phosphoproteome analysis of DLC1 in breast cancer