ArticleOncogene2017
ZEB1 induces LOXL2-mediated collagen stabilization and deposition in the extracellular matrix to drive lung cancer invasion and metastasis.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
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Who cites it
146 citing papers in PubMed, 210 citations in OpenAlex.
- Exploration of Serum Proteomic Profiling and Diagnostic Model That Differentiate Crohn's Disease and Intestinal Tuberculosis.PloS one · 2016Trial
- Label-free, multiphoton microscopy-based strategy for intraoperative grading of lung adenocarcinoma via quantitative extracellular matrix analysis.Biomedical optics express · 2026Article
- Upregulated CCN1 from pleural mesothelial cells alters collagen I conformation and drives fibrosis via ITGB1/MAPK signaling.Cellular & molecular biology letters · 2026Article
- Targeting Wnt3a and Loxl2 Synergistically Induces Ferroptosis in Liver Cancer Stem Cells and Suppresses Tumorigenesis.Cancer science · 2026Article
- Review
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- COL1A1-induced LOXL2 promotes ovarian cancer metastasis via a feedback loop upon inhibiting EGFR lysosomal degradation.Experimental & molecular medicine · 2026Article
- Regulatory network and spatial modeling reveal cooperative mechanisms of resistance and immune escape in ER+ breast cancer.BMC cancer · 2026Article
- Covalent Inhibitor Screening for Targeting LOXL2: Studied by Virtual Screening and Experimental Validation.Recent patents on anti-cancer drug discovery · 2026Article
- Extracellular Matrix-Related Prognostic Signature for Head and Neck Squamous Cell Carcinoma via Multi-Algorithm Survival Modeling.Biomarker insights · 2026Article
- Cancer-associated fibroblasts in the lung cancer microenvironment from multi-dimensional mechanisms to therapeutic strategies.Frontiers in oncology · 2026Review
- The mechano-immunological barrier in fibrosis-associated lung cancer: targeting matrix stiffness and the Piezo1 axis for microenvironment normalization.Frontiers in pharmacology · 2026Review
- Integrative analysis identifies LHFPL6 as a CAF-specific prognostic biomarker in colorectal cancer.Clinical and experimental medicine · 2025Article
- Overexpression of miR-431-5p Inhibits the Development of Hypertrophic Scars by Negatively Regulating the Expression of ZEB1.Journal of cosmetic dermatology · 2025Article
- Pan-cancer analysis of role of LOXL4 and experiment validation in osteosarcoma.Discover oncology · 2025Article
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- Niosome-loaded silibinin and methotrexate for synergistic breast cancer combination chemotherapy: in silico and in vitro study.Cancer cell international · 2025Article
- Regulatory network and spatial modeling reveal cooperative mechanisms of resistance and immune escape in ER+ breast cancer.bioRxiv : the preprint server for biology · 2025Article
- Lung cancer intravasation-on-a-chip: Visualization and machine learning-assisted automatic quantification.Bioactive materials · 2025Article
- GPER1 is involved in shaping tumor immune microenvironment and its expression is decreased in NSCLC tumorigenesis.Scientific reports · 2025Article
86 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Lung cancer is the leading cause of cancer-related deaths, primarily due to distant metastatic disease. Metastatic lung cancer cells can undergo an epithelial-to-mesenchymal transition (EMT) regulated by various transcription factors, including a double-negative feedback loop between the microRNA-200 (miR-200) family and ZEB1, but the precise mechanisms by which ZEB1-dependent EMT promotes malignancy remain largely undefined. Although the cell-intrinsic effects of EMT are important for tumor progression, the reciprocal dynamic crosstalk between mesenchymal cancer cells and the extracellular matrix (ECM) is equally critical in regulating invasion and metastasis. Investigating the collaborative effect of EMT and ECM in the metastatic process reveals increased collagen deposition in metastatic tumor tissues as a direct consequence of amplified collagen gene expression in ZEB1-activated mesenchymal lung cancer cells. In addition, collagen fibers in metastatic lung tumors exhibit greater linearity and organization as a result of collagen crosslinking by the lysyl oxidase (LOX) family of enzymes. Expression of the LOX and LOXL2 isoforms is directly regulated by miR-200 and ZEB1, respectively, and their upregulation in metastatic tumors and mesenchymal cell lines is coordinated to that of collagen. Functionally, LOXL2, as opposed to LOX, is the principal isoform that crosslinks and stabilizes insoluble collagen deposition in tumor tissues. In turn, focal adhesion formation and FAK/SRC signaling is activated in mesenchymal tumor cells by crosslinked collagen in the ECM. Our study is the first to validate direct regulation of LOX and LOXL2 by the miR-200/ZEB1 axis, defines a novel mechanism driving tumor metastasis, delineates collagen as a prognostic marker, and identifies LOXL2 as a potential therapeutic target against tumor progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.