Identification of HSPG2 as a bladder pro-tumor protein through NID1/AKT signaling.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39438949", "kind": "science-record", "revision": 4, "content_hash": "sha256:016b8105eb809645015804cf12049f7a75c73906ad5adb9e95cbd531f4f215aa", "created_at": "2026-11-01T20:29:42Z", "updated_at": "2026-11-01T22:55:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of HSPG2 as a bladder pro-tumor protein through NID1/AKT signaling.", "doi": "10.1186/s12935-024-03527-7", "pmid": "39438949", "authors": ["Cong Li", "Pengwei Luo", "Fengzhu Guo", "Xu Jia", "Min Shen", "Ting Zhang", "Shusen Wang", "Ting Du"], "journal": "Cancer cell international", "year": 2024, "abstract": "PURPOSE: Heparan sulfate proteoglycans (HSPGs) are complex molecules found on the cell membrane and within the extracellular matrix, increasingly recognized for their role in tumor progression. This study aimed to investigate the involvement of Heparan sulfate proteoglycan 2 (HSPG2) in the progression of bladder cancer.\nMETHODS: We identified HSPG2 as a promoter of bladder tumor progression using single-cell RNA sequencing and transcriptome analysis of sequencing data from seven patient samples obtained from the Gene Expression Omnibus (GEO) database (GSE135337). Transcript profiles of 28 normal tissues and 407 bladder tumor tissues were analyzed for HSPG2 expression and survival outcomes using the Sanger tools and cBioPortal databases. HSPG2-overexpressing T24 and Biu-87 cell lines were generated, and cell proliferation and migration were assessed using CCK-8 and Transwell assays. Western blotting and immunostaining were performed to evaluate the activation of Nidogen-1 (NID1)/protein kinase B (AKT) signaling. Mouse models with patient-derived tumor organoids (HSPG2high and HSPG2low) were established to assess anticancer effects.\nRESULTS: Our results demonstrated a marked upregulation of HSPG2 in malignant bladder tumors, which correlated significantly with poor patient prognosis. HSPG2 overexpression consistently enhanced bladder tumor cell proliferation and conferred chemotherapy resistance, as shown in both in vitro and in vivo experiments. Mechanistically, HSPG2 upregulated NID1 expression, leading to the activation of the AKT pro-survival signaling pathway and promoting sustained tumor growth in bladder cancer.\nCONCLUSION: This study highlights the critical pro-tumor role of HSPG2/NID1/AKT signaling in bladder cancer and suggests its potential as a therapeutic target in clinical treatment.", "claims": [{"id": "claim-method", "statement": "The differences between two groups were compared using an independent T test. Comparisons among multiple groups were analyzed using one-way ANOVA, followed by Tukey’s post hoc test. The Kaplan–Meier estimator was conducted to evaluate the overall survival.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39438949", "locator": "sections[15] \"Statistical analysis\" paragraph 2", "quote": "The differences between two groups were compared using an independent T test. Comparisons among multiple groups were analyzed using one-way ANOVA, followed by Tukey’s post hoc test. The Kaplan–Meier estimator was conducted to evaluate the overall survival."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data generated and analyzed in this study are included in the manuscript and supplementary files. 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