LAMC1 upregulation via TGFβ induces inflammatory cancer-associated fibroblasts in esophageal squamous cell carcinoma via NF-κB-CXCL1-STAT3.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34218518", "kind": "science-record", "revision": 6, "content_hash": "sha256:53645d7155438d24c3848f20f96525f5028fbe7a201914cbdc6e926896a12cb8", "created_at": "2026-11-01T15:41:41Z", "updated_at": "2026-11-01T21:25:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "LAMC1 upregulation via TGFβ induces inflammatory cancer-associated fibroblasts in esophageal squamous cell carcinoma via NF-κB-CXCL1-STAT3.", "doi": "10.1002/1878-0261.13053", "pmid": "34218518", "authors": ["Lingling Fang", "Yun Che", "Chaoqi Zhang", "Jianbing Huang", "Yuanyuan Lei", "Zhiliang Lu", "Nan Sun", "Jie He"], "journal": "Molecular oncology", "year": 2021, "abstract": "Cancer-associated fibroblasts (CAF) are a heterogeneous cell population within the tumor microenvironment,and play an important role in tumor development. By regulating the heterogeneity of CAF, transforming growth factor β (TGFβ) influences tumor development. Here, we explored oncogenes regulated by TGFβ1 that are also involved in signaling pathways and interactions within the tumor microenvironment. We analyzed sequencing data of The Cancer Genome Atlas (TCGA) and our own previously established RNA microarray data (GSE53625), as well as esophageal squamous cell carcinoma (ESCC) cell lines with or without TGFβ1 stimulation. We then focused on laminin subunit gamma 1 (LAMC1), which was overexpressed in ESCC cells, affecting patient prognosis, which could be upregulated by TGFβ1 through the synergistic activation of SMAD family member 4 (SMAD4) and SP1. LAMC1 directly promoted the proliferation and migration of tumor cells, mainly via Akt-NFκB-MMP9/14 signaling. Additionally, LAMC1 promoted CXCL1 secretion, which stimulated the formation of inflammatory CAF (iCAF) through CXCR2-pSTAT3. Inflammatory CAF promoted tumor progression. In summary, we identified the dual mechanism by which the upregulation of LAMC1 by TGFβ in tumor cells not only promotes ESCC proliferation and migration, but also indirectly induces carcinogenesis by stimulating CXCL1 secretion to promote the formation of iCAF. This finding suggests that LAMC1 could be a potential therapeutic target and prognostic marker for ESCC.", "claims": [{"id": "claim-data-access", "statement": "The data that support the findings of this study are available from the corresponding author (prof.jiehe@gmail.com) upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34218518", "locator": "sections[34] \"Data accessibility\" paragraph 2", "quote": "The data that support the findings of this study are available from the corresponding author (prof.jiehe@gmail.com) upon reasonable request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:34218518"], "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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HEsoS105Su01, Shanghai, China) for immunohistochemistry; 12 fresh ESCC tissues were obtained at our"], "order_basis": "paper_text_order:1827", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["(MRC‐5; KG508, Keygene, Nanjing, China) was cultured in MEM (minimum Eagle’s medium), with 10% FBS,"], "order_basis": "paper_text_order:2435", "id": "assay:2"}, {"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": ["TCTTATGA‐3’) were inserted into pLV‐Puro for knockdown SP1 (SyngenTech, Beijing, China), two shRNA", "AGTACTTCA‐3’) were inserted into pLV‐neo for knockdown SMAD4 (SyngenTech) and two shRNA oligonucleo", "were inserted into pLV‐Puro (SyngenTech) for knockdown LAMC1. The negative control (NC) sequence wa", "1. As previous descried, we then constructed knockdown SP1, knockdown SMAD4, knockdown SP1 combined"], "order_basis": "paper_text_order:2684", "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": ["cted cells was confirmed by quantitative (RT‐qPCR) and western blot, 96 h after infection. Sta"], "order_basis": "paper_text_order:3588", "id": "assay:4"}, {"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": ["was confirmed by quantitative (RT‐qPCR) and western blot, 96 h after infection. Statistical analysis"], "order_basis": "paper_text_order:3599", "id": "assay:5"}]}