Deubiquitylase YOD1 regulates CDK1 stability and drives triple-negative breast cancer tumorigenesis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37667382", "kind": "science-record", "revision": 4, "content_hash": "sha256:ffeeed1a0302aa4d5023a00819a9ba4eefb6e1bca3da1e76e4a52bec06dc143d", "created_at": "2026-11-01T19:02:27Z", "updated_at": "2026-11-01T22:52:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Deubiquitylase YOD1 regulates CDK1 stability and drives triple-negative breast cancer tumorigenesis.", "doi": "10.1186/s13046-023-02781-3", "pmid": "37667382", "authors": ["Zhitao Han", "Qi Jia", "Jing Zhang", "Miaomiao Chen", "Lining Wang", "Kai Tong", "Weiwei He", "Yajie Zhang", "Weina Zhu", "Ju Qin", "Tao Wang", "Tielong Liu", "Yong Ma", "Yuanming Chen", "Siluo Zha", "Chunlei Zhang"], "journal": "Journal of experimental & clinical cancer research : CR", "year": 2023, "abstract": "BACKGROUND: Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with the initiation and progression of Triple-negative breast cancer (TNBC). The publicly available TCGA database of breast cancer data was used to analyze the OTUD deubiquitinating family members that were correlated with survival of breast cancer and ovarian tumor domain-containing 2 (OTUD-2), or YOD1 was identified. The aim of present study was to assess YOD1 expression and function in human TNBC and then explored the underlying molecular events.\nMETHODS: We detected the expression of YOD1 in 32 TNBC and 44 NTNBC samples by qRT-PCR, Western blot and immunohistochemistry. Manipulation of YOD1 expression was assessed in vitro and in vivo for TNBC cell proliferation, migration, invasion, cell-cycle and drug resistance, using colony formation assay, transwell assay, CCK8 assay, TUNEL assay, flow cytometric analysis and xenograft tumor assay. Next, proteomic analysis, Western blot, proximity ligation assay, Immunoprecipitation, and Immunofluorescence were conducted to assess downstream targets.\nRESULTS: It was found that YOD1 was significantly upregulated in TNBC tissues compared with non-triple-negative breast cancer (NTNBC), which was positively correlated with poor survival in TNBC patients. Knockdown of YOD1 effectively inhibited TNBC cell migration, proliferation, cell cycle and resistance to cisplatin and paclitaxel. Mechanistically, YOD1 promoted TNBC progression in a manner dependent on its catalytic activity through binding with CDK1, leading to de-polyubiquitylation of CDK1 and upregulation of CDK1 expression. In addition, YOD1 overexpression was found to be correlated with CDK1 overexpression in human TNBC specimens. Finally, in vivo study demonstrated that YOD1 knockdown or YOD1 inhibitor could inhibit CDK1 expression and suppress the growth and metastasis of TNBC tumors.\nCONCLUSION: Our study highlights that YOD1 functions as an oncogene in TNBC via binding to CDK1 and mediated its stability and oncogenic activity. Interfering with YOD1 expression or YOD1 inhibitor could suppress TNBC cells in vitro and in vivo, suggesting that YOD1 may prove to be a promising therapeutic target for TNBC.", "claims": [{"id": "claim-method", "statement": "Survival curves were plotted using the Kaplan-Meier method and compared using log-rank tests.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37667382", "locator": "sections[23] \"Statistical analysis\" paragraph 2", "quote": "Survival curves were plotted using the Kaplan-Meier method and compared using log-rank tests."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The authors declare that all data and materials supporting the findings of this study are available in this article and its supplementary files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37667382", "locator": "sections[39] \"Data Availability\" paragraph 2", "quote": "The authors declare that all data and materials supporting the findings of this study are available in this article and its supplementary files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Higher YOD1 expression was associated with a lower overall survival rate in TNBC patients (p = 0.031).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37667382", "locator": "sections[25] \"YOD1 upregulation is inversely correlated with poor prognosis in TNBC\" paragraph 2", "quote": "It was found that higher YOD1 expression level (scored at 3) was related to a lower overall survival rate (Fig. 1E, p = 0.031) and higher proportion of TNBC patients (p < 0.001, Table 1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Higher YOD1 expression was associated with a lower overall survival rate in TNBC patients (p = 0.031).", "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:37667382"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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Manipulation of YO", "graft tumor assay. Next, proteomic analysis, Western blot, proximity ligation assay, Immunoprecipitati", "in 2 TNBC tissues and 9 none-TNBC tissues by Western blotting Supplementary Material 2: Figure S2. Express", "vels were detected in the indicated cells by Western blotting. C, YOD1 expression were evaluated in the in"], "order_basis": "paper_text_order:717", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["4 NTNBC samples by qRT-PCR, Western blot and immunohistochemistry. Manipulation of YOD1 expression was assesse", "ity ligation assay, Immunoprecipitation, and Immunofluorescence were conducted to assess downstream targets.", "were evaluated in the indicated cells using immunohistochemistry. Data are mean ± SEM. Scale bars, 20 μm Supp", "ns. Detected the YOD1 and CDK1 expression by immunohistochemistry. Scale bars, 100 μm or 20 μm Supplementary M"], "order_basis": "paper_text_order:733", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["of YOD1 expression was assessed in vitro and in vivo for TNBC cell proliferation, migration, inva", "expression in human TNBC specimens. Finally, in vivo study demonstrated that YOD1 knockdown or YO", "bitor could suppress TNBC cells in vitro and in vivo, suggesting that YOD1 may prove to be a prom"], "order_basis": "paper_text_order:813", "id": "assay:3"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ing colony formation assay, transwell assay, CCK8 assay, TUNEL assay, flow cytometric analysis", "tary Material 3: Figure S3. The detection of apoptosis level in MCF-10 A by flow cytometry with YOD", "10 µM cisplatin or 50 nM paclitaxel induced apoptosis of the indicated MCF-10 A cells. Data are me", "ffect of YOD1. B, Flow cytometry analysis of apoptosis suggests that CDK1 inhibitors could signific"], "order_basis": "paper_text_order:950", "id": "assay:4"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["y, transwell assay, CCK8 assay, TUNEL assay, flow cytometric analysis and xenograft tumor assay. Next, pr", "detection of apoptosis level in MCF-10 A by flow cytometry with YOD1 overexpression or knockdown. A, Va", "CF-10 A cells by western blotting assays. B, Flow cytometry assays were performed to evaluate the effect", "e proliferation promoting effect of YOD1. B, Flow cytometry analysis of apoptosis suggests that CDK1 inh"], "order_basis": "paper_text_order:975", "id": "assay:5"}, {"role": "data_generation", "definition_id": "mass_spectrometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ic analysis and xenograft tumor assay. Next, proteomic analysis, Western blot, proximity ligation a", "AG group or pcDNA3.1- group were analyzed by LC-MS/MS Supplementary Material 5: Figure S5. YOD1 in"], "order_basis": "paper_text_order:1033", "id": "assay:6"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["related with poor survival in TNBC patients. Knockdown of YOD1 effectively inhibited TNBC cell migr", "inally, in vivo study demonstrated that YOD1 knockdown or YOD1 inhibitor could inhibit CDK1 express", "cells. A, VN173-YOD1 and VC155-CDK1 were co-transfected into 293T cells and detected by BiFC. The si", "UD, T-ZnF) and VC155-CDK1 constructs were co-transfected into 293T cells and detected the BiFC signal"], "order_basis": "paper_text_order:1386", "id": "assay:7"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Survival curves were plotted using the Kaplan-Meier method and compared using log-rank tests."], "order_basis": "consumes_earlier_output", "id": "assay:8"}]}