Hippo component YAP promotes focal adhesion and tumour aggressiveness via transcriptionally activating THBS1/FAK signalling in breast cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30055645", "kind": "science-record", "revision": 8, "content_hash": "sha256:1d2750c059173de25fc63067d590556c69973d6b70ebfaceaaeb63809f75086c", "created_at": "2026-11-01T15:40:36Z", "updated_at": "2026-11-01T22:43:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Hippo component YAP promotes focal adhesion and tumour aggressiveness via transcriptionally activating THBS1/FAK signalling in breast cancer.", "doi": "10.1186/s13046-018-0850-z", "pmid": "30055645", "authors": ["Jie Shen", "Beibei Cao", "Yatao Wang", "Chenshen Ma", "Zhuo Zeng", "Liang Liu", "Xiaolan Li", "Deding Tao", "Jianping Gong", "Daxing Xie"], "journal": "Journal of experimental & clinical cancer research : CR", "year": 2018, "abstract": "BACKGROUND: Focal adhesion plays an essential role in tumour invasiveness and metastasis. Hippo component YAP has been widely reported to be involved in many aspects of tumour biology. However, its role in focal adhesion regulation in breast cancer remains unexplored.\nMETHODS: Tissue microarray was used to evaluate YAP expression in clinical breast cancer specimens by immunohistochemical staining. Cell migration and invasion abilities were measured by Transwell assay. A cell adhesion assay was used to measure the ability of cell adhesion to gelatin. The focal adhesion was visualized through immunofluorescence. Phosphorylated FAK and other proteins were detected by Western blot analysis. Gene expression profiling was used to screen differently expressed genes, and gene ontology enrichment was performed using DAVID software. The gene mRNA levels were measured by quantitative real-time PCR. The activity of the THBS1-promoter was evaluated by dual luciferase assay. Chromatin immunoprecipitation (ChIP) was used to verify whether YAP could bind to the THBS1-promoter region. The prediction of potential protein-interaction was performed with the String program. The ChIP sequence data of TEAD was obtained from the ENCODE database and analysed via the ChIP-seek tool. The gene expression dataset (GSE30480) of purified tumour cells from primary breast tumour tissues and metastatic lymph nodes was used in the gene set enrichment analysis. Prognostic analysis of the TCGA dataset was performed by the SurvExpress program. Gene expression correlation of the TCGA dataset was analysed via R2: Genomics Analysis and Visualization Platform.\nRESULTS: Our study provides evidence that YAP acts as a promoter of focal adhesion and tumour invasiveness via regulating FAK phosphorylation in breast cancer. Further experiments reveal that YAP could induce FAK phosphorylation through a TEAD-dependent manner. Using gene expression profiling and bioinformatics analysis, we identify the FAK upstream gene, thrombospondin 1, as a direct transcriptional target of YAP-TEAD. Silencing THBS1 could reverse the YAP-induced FAK activation and focal adhesion.\nCONCLUSION: Our results unveil a new signal axis, YAP/THBS1/FAK, in the modulation of cell adhesion and invasiveness, and provides new insights into the crosstalk between Hippo signalling and focal adhesion.", "claims": [{"id": "claim-method", "statement": "All continuous data are presented as the mean ± SD and statistically analysed with Student’s t-test (two-tailed) and analysis of variance (ANOVA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30055645", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "All continuous data are presented as the mean ± SD and statistically analysed with Student’s t-test (two-tailed) and analysis of variance (ANOVA)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data can be provided upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30055645", "locator": "sections[28] \"Availability of data and materials\" paragraph 2", "quote": "All data can be provided upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "YAP promotes focal adhesion and tumour invasiveness in breast cancer through a YAP/THBS1/FAK signalling axis. Statistical analysis used two-tailed Student’s t-test and ANOVA in SPSS version 19.0, with p < 0.05 considered statistically significant; the source data are available from the authors upon request.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:30055645", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Our study provides evidence that YAP acts as a promoter of focal adhesion and tumour invasiveness via regulating FAK phosphorylation in breast cancer."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "YAP promotes focal adhesion and tumour invasiveness in breast cancer through a YAP/THBS1/FAK signalling axis. Statistical analysis used two-tailed Student’s t-test and ANOVA in SPSS version 19.0, with p < 0.05 considered statistically significant; the source data are available from the authors upon request.", "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:30055645"], "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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METHODS: Tissue microarray was used to evaluate YAP expression in clini", "cancer specimens from a breast cancer tissue microarray. The expression level of YAP was significant"], "order_basis": "paper_text_order:382", "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": ["ssion in clinical breast cancer specimens by immunohistochemical staining. Cell migration and invasion abilit", "n. The focal adhesion was visualized through immunofluorescence. Phosphorylated FAK and other proteins were", "101 paired specimens were analysed. Through immunohistochemistry staining, we found that the YAP expression l", "oor prognosis in breast cancer patients. (a) Immunohistochemistry staining of YAP protein in paired primary an"], "order_basis": "paper_text_order:468", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ated FAK and other proteins were detected by Western blot analysis. Gene expression profiling was used"], "order_basis": "paper_text_order:770", "id": "assay:3"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ne mRNA levels were measured by quantitative real-time PCR. The activity of the THBS1-promoter was eval"], "order_basis": "paper_text_order:983", "id": "assay:4"}, {"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": ["Materials and methods Cell culture and transfection Human breast cancer cell lines MDA-MB-231, M", "ons were performed using Lipofectamine® 2000 transfection reagent (Thermo Fisher, Cat. #11668019), acc", "overexpression of YAP and its mutants. After transfection, the cells were treated with 500 μg/ml G418", "escribed in Additional file 1: Table S1. The siRNA transfections were performed using Lipofecta"], "order_basis": "paper_text_order:2502", "id": "assay:5"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["le medium (DMEM, KeyGEN), and the MDA-MB-231 cell line was maintained in Leibovitz’s L-15 medium (L15, KeyGEN). DM", "e HEK293T and MCF7 cell lines were routinely cultured in Dulbecco’s modified Eagle medium (DMEM, KeyG", "n Human breast cancer cell lines MDA-MB-231, MCF7 and human embryonic kidney cell line HEK293T", "e Culture Collection (ATCC). 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