Knockdown of SPON2 inhibits the growth of triple-negative breast cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36959811", "kind": "science-record", "revision": 3, "content_hash": "sha256:149fc921cd917458a8a3687cd995fb6fdf86b1de828f2bff3206d15356941f7e", "created_at": "2026-11-01T19:01:36Z", "updated_at": "2026-11-01T22:09:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Knockdown of SPON2 inhibits the growth of triple-negative breast cancer.", "doi": "10.3389/fonc.2023.1141417", "pmid": "36959811", "authors": ["Xueyi Hu", "Caiwu Su", "Jian Wei"], "journal": "Frontiers in oncology", "year": 2023, "abstract": "Objective: Spondin-2 (SPON2) is highly expressed in a variety of tumors and has been associated with poor prognosis, but the relationship to triple-negative breast cancer (TNBC) is unclear. The aim of this study is to investigate the expression of SPON2 in TNBC and its function.\nMethods: Immunohistochemistry was used to detect the expression of the SPON2 protein in TNBC and in normal tissue adjacent to cancer and breast fibroadenoma. The GEO database GSE76275 dataset was used to study the expression of SPON2 mRNA in TNBC and non-TNBC. ​The expression of SPON2 mRNA was detected by qPCR in TNBC cells MDA-MB-231, non-TNBC breast cancer cells MCF-7, and normal breast cells MCF-10A. ​Kaplan Meier-Plotter database was used to analyze the relationship between SPON2 expression and TNBC prognosis. ​ShRNA lentivirus was used to knock down high expression of SPON2 in TNBC cells. The effects of knockdown of SPON2 expression on the proliferation, migration, invasion, apoptosis, and subcutaneous tumorigenic ability of TNBC cells in nude mice were analyzed using CCK8, clone formation assay, scratch assay, transwell migration assay, transwell invasion assay, Hoechst apoptosis assay, and tumorigenic ability in nude mice. Transcriptome sequencing of TNBC cells with knockdown SPON2 expression. ​In combination with the GEO database, GO and KEGG analyses were performed, and psychophysiological interaction Protein-Protein Interaction Networks (PPI) analysis was performed for transcriptome sequencing of the differentially expressed genes. ​The changes in the expression of PI3K-ATK pathway proteins after SPON2 knockdown were detected by Western blot.\nResults: Our study shows that upregulation of SPON2 in TNBC is associated with poorer patient outcomes. Knockdown of SPON2 inhibited TNBC cell proliferation, clone formation, migration, invasion, and tumorigenic ability and promoted apoptosis. Knockdown of SPON2 up-regulated TNBC cell adhesion and down-regulated PI3K-ATK pathway, and PPI results showed that CCL2 was the key protein.\nConclusions: SPON2 may be a valuable biomarker for the diagnosis and prognosis of TNBC and is a potential therapeutic target for TNBC.", "claims": [{"id": "claim-method", "statement": "To investigate the effect of high SPON2 expression in TNBC on its prognostic RFS, we performed an analysis using the Kaplan-Meier Plotter database, which showed that high SPON2 expression in TNBC had worse RFS, Figure 1E .", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36959811", "locator": "sections[21] \"SPON2 expression is up-regulated in TNBC and correlates with poor prognosis\" paragraph 4", "quote": "To investigate the effect of high SPON2 expression in TNBC on its prognostic RFS, we performed an analysis using the Kaplan-Meier Plotter database, which showed that high SPON2 expression in TNBC had worse RFS, Figure 1E ."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36959811", "locator": "sections[30] \"Data availability statement\" paragraph 2", "quote": "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation."}], "state": "complete"}, {"id": "claim-target-result", "statement": "SPON2 is up-regulated in TNBC and is associated with poor patient prognosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36959811", "locator": "sections[1] \"Introduction\" paragraph 6", "quote": "This study confirms that SPON2 is up-regulated in TNBC and is associated with poor patient prognosis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "SPON2 is up-regulated in TNBC and is associated with poor patient prognosis.", "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:36959811"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE103091"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE103091"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36959811", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2023.1141417", "sha256": 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The effects of knockdown of SPON2 expression on the proliferation, mi", "Transcriptome sequencing of TNBC cells with knockdown SPON2 expression. ​In combination with the G", "ion of PI3K-ATK pathway proteins after SPON2 knockdown were detected by Western blot. Results: Our"], "order_basis": "paper_text_order:0", "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": 0.93, "evidence": ["of SPON2 in TNBC and its function. 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Knockdown of SPON2 up-regulated TNBC cell a", "TNBC cells in nude mice were analyzed using CCK8, clone formation assay, scratch assay, trans"], "order_basis": "paper_text_order:997", "id": "assay:5"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["us tumorigenic ability of TNBC cells in nude mice were analyzed using CCK8, clone formation assay,"], "order_basis": "paper_text_order:1067", "id": "assay:6"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.83, "evidence": ["assay, and tumorigenic ability in nude mice. Transcriptome sequencing of TNBC cells with knockdown SPON", "on Networks (PPI) analysis was performed for transcriptome sequencing of the differentially expressed g"], "order_basis": "paper_text_order:1252", "id": "assay:7"}, {"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": ["teins after SPON2 knockdown were detected by Western blot. Results: Our study shows that upregulation"], "order_basis": "paper_text_order:1669", "id": "assay:8"}, {"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": ["To investigate the effect of high SPON2 expression in TNBC on its prognostic RFS, we performed an analysis using the Kaplan-Meier Plotter database, which showed that high SPON2 expression in TNBC had worse RFS, Figure 1E ."], "order_basis": "consumes_earlier_output", "id": "assay:9"}]}