Quantitative phosphoproteomic analysis identifies novel functional pathways of tumor suppressor DLC1 in estrogen receptor positive breast cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30278072", "kind": "science-record", "revision": 7, "content_hash": "sha256:0d9f7a3b66fe6981b7abde6b2fed1074f414333fd01f54e7149506433e2e6795", "created_at": "2026-11-01T15:40:37Z", "updated_at": "2026-11-01T22:00:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Quantitative phosphoproteomic analysis identifies novel functional pathways of tumor suppressor DLC1 in estrogen receptor positive breast cancer.", "doi": "10.1371/journal.pone.0204658", "pmid": "30278072", "authors": ["Yesim Gökmen-Polar", "Jason D True", "Edyta Vieth", "Yuan Gu", "Xiaoping Gu", "Guihong D Qi", "Amber L Mosley", "Sunil S Badve"], "journal": "PloS one", "year": 2018, "abstract": "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. Low expression of DLC1 correlates with poor prognosis in patients with ER+ breast cancer with further decrease in metastatic lesions. The Cancer Genome Atlas (TCGA) data showed that down regulation of DLC1 is not due to methylation or mutations. To seek further insights in understanding the role of DLC1 in ER+ breast cancer, we stably overexpressed DLC1-full-length (DLC1-FL) in T-47D breast cancer cells; this inhibited cell colony formation significantly in vitro compared to its control counterpart. Label-free global proteomic and TiO2 phosphopeptide enrichment assays (ProteomeXchange identifier PXD008220) showed that 205 and 122 phosphopeptides were unique to DLC1-FL cells and T-47D-control cells, respectively, whereas 6,726 were quantified by phosphoproteomics analysis in both conditions. The top three significant clusters of differentially phosphopeptides identified by DAVID pathway analysis represent cell-cell adhesion, mRNA processing and splicing, and transcription regulation. Phosphoproteomics analysis documented an inverse relation between DLC1 expression and several phosphopeptides including epithelial cell transforming sequence 2 (ECT2). Decreased phosphorylation of ECT2 at the residue T359, critical for its active conformational change, was validated by western blot. In addition, the ECT2 T359-containing phosphopeptide was detected in both basal and luminal patient-derived breast cancers breast cancer phosphoproteomics data on the Clinical Proteomic Tumor Analysis Consortium (CPTAC) Assay portal. Together, for the first time, this implicates ECT2 phosphorylation in breast cancer, which has been proposed as a therapeutic target in lung cancer. In conclusion, this data suggests that low expression of DLC1 is associated with poor prognosis. Targeting ECT2 phosphopeptides could provide a promising mechanism for controlling poor prognosis seen in DLC1low ER+ breast cancer.", "claims": [{"id": "claim-method", "statement": "The Kaplan-Meier survival analysis was calculated using Cox proportional hazard model, and the score test of the proportional hazard model is equivalent to the log-rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30278072", "locator": "sections[3] \"Analysis of publicly available datasets\" paragraph 2", "quote": "The Kaplan-Meier survival analysis was calculated using Cox proportional hazard model, and the score test of the proportional hazard model is equivalent to the log-rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the proteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD008220 and 10.6019/PXD008220\".", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30278072", "locator": "sections[28] \"Data Availability\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited to the proteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD008220 and 10.6019/PXD008220\"."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30278072"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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