ArticleInternational journal of cancer2025
FHL2 expression by cancer-associated fibroblasts promotes metastasis and angiogenesis in lung adenocarcinoma.
Article in International journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Correction to "FHLInternational journal of cancer · 2026Article
- Deciphering the Transcription Factor-Dominated Ecosystem During Esophageal Squamous Cell Carcinoma Progression at the Single-Cell Level.International journal of molecular sciences · 2026Article
- CD81 promotes proliferation and predicts survival in lung squamous cell carcinoma.Clinical and translational medicine · 2026Article
- Integrative Single-Cell and Machine Learning Analysis Identifies an EMT-Associated Prognostic Signature for Papillary Thyroid Cancer.Cancer medicine · 2026Article
- Cancer-Associated Fibroblasts Functions as Multifunctional Architects of the Tumor Stroma and Represent Emerging Therapeutic Vulnerabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Advances in Metabolic Reprogramming and Immune Regulatory Mechanisms in Lung Cancer.Oncology research · 2026Review
- Cancer-associated fibroblasts in the tumor microenvironment: heterogeneity, crosstalk mechanisms, and therapeutic implications.Molecular cancer · 2025Review
- Targeting CAF-specific metabolic pathways in breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Cancer-Associated Fibroblasts: Origin, Classification, Tumorigenicity, and Targeting for Cancer Therapy.MedComm · 2025Review
- Temporal vascular pattern remodeling mediated by the FHL2/sFRP2 signaling pathway in tenocytes affects tendon repair and regeneration.Experimental & molecular medicine · 2025Article
- FHL2 enhances ITGB1-mediated ECM remodeling and cellular stiffness to promote radioresistance in non-small cell lung cancer.Cell death discovery · 2025Article
- [Prediction of Spatial Distance of CAFs-TAECs for Pathological Response to Neoadjuvant Chemoimmunotherapy in Lung Squamous Cell Carcinoma].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Article
- Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.MedComm · 2025Review
- [Epithelial-mesenchymal Transition: Biological Basis and Clinical Prospects of Lung Cancer Invasion, Metastasis, and Drug Resistance].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- FHL2 expression by cancer-associated fibroblasts promotes metastasis and angiogenesis in lung adenocarcinoma.International journal of cancer · 2025Article
- Danggui Buxue Decoction attenuates 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung cancer growth in A/J mice by suppressing HIF-1α/VEGF-mediated angiogenesis.Frontiers in medicine · 2025Article
- Promotion Mechanisms of Stromal Cell-Mediated Lung Cancer Development Within Tumor Microenvironment.Cancer management and research · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
Abstract
Cancer-associated fibroblasts (CAFs) contribute to the progression of lung cancer. Four and a half LIM domain protein-2 (FHL2) is a component of focal adhesion structures. We analyzed the function of FHL2 expressed by CAFs in lung adenocarcinoma. Expression of FHL2 in fibroblast subtypes was investigated using database of single-cell RNA-sequencing of lung cancer tissue. The role of FHL2 in the proliferation and migration of CAFs was assessed. The effects of FHL2 knockout on the migration and invasion of human lung adenocarcinoma cells and tube formation of endothelial cells induced by CAF-conditioned medium (CM) were evaluated. The effect of FHL2 knockout in CAFs on metastasis was determined using a murine orthotopic lung cancer model. The prognostic significance of stromal FHL2 was assessed by immunohistochemistry in human adenocarcinoma specimens. FHL2 is highly expressed in myofibroblasts in cancer tissue. TGF-β1 upregulated FHL2 expression in CAFs and FHL2 knockdown attenuated CAF proliferation. FHL2 knockout reduced CAF induced migration of A110L and H23 human lung adenocarcinoma cell lines, and the induction of tube formation of endothelial cells. FHL2 knockout reduced CAF-induced metastasis of lung adenocarcinomas in an orthotopic model in vivo. The concentration of Osteopontin (OPN) in CM from CAF was downregulated by FHL2 knockout. siRNA silencing and antibody blocking of OPN reduced the pro-migratory effect of CM from CAF on lung cancer cells. In resected lung adenocarcinoma specimens, positive stromal FHL2 expression was significantly associated with higher microvascular density and worse prognosis. In conclusion, FHL2 expression by CAFs enhances the progression of lung adenocarcinoma by promoting angiogenesis and metastasis.
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