ArticleThe Journal of clinical investigation2015
Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 185 citations in OpenAlex.
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- Review
- Recombinant Production and Characterization of Human Enzymes Responsible for Collagen Lysine Post-translational Modifications.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Plexin A2 Knockdown Enhances Apoptosis in Chemotherapy Treated Melanoma Cells.Oncology research · 2026Article
- The roles of cell cycle proteins in regulating the tumor immune microenvironment.Genes & diseases · 2026Review
- TAGLN: a stiffness-driven prognostic biomarker for metastatic colorectal cancer.Cancer cell international · 2025Article
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
- Engineering a Human-Sized Common Bile Duct Prototype with Regenerative Potential: In Vitro Evaluation of Mechanics, Function, Degradation, and Immune Modulation.Advanced healthcare materials · 2025Article
- Structural basis of collagen glucosyltransferase function and its serendipitous role in kojibiose synthesis.Nature communications · 2025Article
- MicroRNA-1303 in cancer pathogenesis and therapy: clinical implications for biomarker development and targeted treatment strategies.Cancer cell international · 2025Review
- Extracellular matrix dynamics in tumor immunoregulation: from tumor microenvironment to immunotherapy.Journal of hematology & oncology · 2025Review
- High extracellular matrix stiffness upregulates TNNT1 to awaken dormant tumor cells in liver metastatic niches of gastric cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer.Experimental hematology & oncology · 2025Review
- Lysyl hydroxylase 2 glucosylates collagen VI to drive lung cancer progression.The Journal of clinical investigation · 2025Article
- Unveiling Matrix Metalloproteinase 13's Dynamic Role in Breast Cancer: A Link to Physical Changes and Prognostic Modulation.International journal of molecular sciences · 2025Review
- Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer.Bioengineering & translational medicine · 2025Review
- Research progress on the role of biomechanical clues in the progression of lung cancer.Frontiers in cell and developmental biology · 2025Review
- Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targets.Molecular biomedicine · 2024Review
53 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 7 institutions in 2 countries.
Funding
Abstract
Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. However, the biochemical nature of collagen cross-links in cancer is still unclear. Here, we postulated that epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen cross-links. Utilizing resected human lung cancer tissues and a p21CIP1/WAF1-deficient, K-rasG12D-expressing murine metastatic lung cancer model, we showed that, relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde-derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde-derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Gain- and loss-of-function studies in tumor cells showed that lysyl hydroxylase 2 (LH2), which hydroxylates telopeptidyl lysine residues on collagen, shifted the tumor stroma toward a high-HLCC, low-LCC state, increased tumor stiffness, and enhanced tumor cell invasion and metastasis. Together, our data indicate that LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma.
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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.