ArticleCommunications biology2021
A collagen glucosyltransferase drives lung adenocarcinoma progression in mice.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Molecular basis of collagen galactosylation by GLT25D1.Nature communications · 2026Article
- Collagen IV biosynthesis: Intracellular choreography of post-translational modifications.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Structural basis of collagen glucosyltransferase function and its serendipitous role in kojibiose synthesis.Nature communications · 2025Article
- The Crystal Structure ofBiochemistry · 2025Article
- Structure of an FeActa crystallographica. Section F, Structural biology communications · 2025Article
- Cloning, expression, and characterization of collagen galactosyltransferases from human, sponge, and sea walnut.Protein expression and purification · 2025Article
- Lysyl hydroxylase 2 glucosylates collagen VI to drive lung cancer progression.The Journal of clinical investigation · 2025Article
- The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation.Nature communications · 2025Article
- Glycosylation Modulates the Structure and Functions of Collagen: A Review.Molecules (Basel, Switzerland) · 2024Review
- Unleashing the Potential of 1,3-Diketone Analogues as Selective LH2 Inhibitors.ACS medicinal chemistry letters · 2023Article
- Identification of Regulatory Molecular "Hot Spots" for LH/PLOD Collagen Glycosyltransferase Activity.International journal of molecular sciences · 2023Review
- Comparative genomic and biochemical analyses identify a collagen galactosylhydroxylysyl glucosyltransferase from Acanthamoeba polyphaga mimivirus.Scientific reports · 2022Article
- Lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes.Scientific reports · 2022Article
- Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic Cancers.Cancers · 2022Review
- Review
- A FeFrontiers in molecular biosciences · 2022Article
- Lysyl hydroxylase 2-induced collagen cross-link switching promotes metastasis in head and neck squamous cell carcinomas.Neoplasia (New York, N.Y.) · 2021Article
Corrections and comments
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Authors and funding
23 authors at 5 institutions in 1 country.
Funding
Abstract
Cancer cells are a major source of enzymes that modify collagen to create a stiff, fibrotic tumor stroma. High collagen lysyl hydroxylase 2 (LH2) expression promotes metastasis and is correlated with shorter survival in lung adenocarcinoma (LUAD) and other tumor types. LH2 hydroxylates lysine (Lys) residues on fibrillar collagen's amino- and carboxy-terminal telopeptides to create stable collagen cross-links. Here, we show that electrostatic interactions between the LH domain active site and collagen determine the unique telopeptidyl lysyl hydroxylase (tLH) activity of LH2. However, CRISPR/Cas-9-mediated inactivation of tLH activity does not fully recapitulate the inhibitory effect of LH2 knock out on LUAD growth and metastasis in mice, suggesting that LH2 drives LUAD progression, in part, through a tLH-independent mechanism. Protein homology modeling and biochemical studies identify an LH2 isoform (LH2b) that has previously undetected collagen galactosylhydroxylysyl glucosyltransferase (GGT) activity determined by a loop that enhances UDP-glucose-binding in the GLT active site and is encoded by alternatively spliced exon 13 A. CRISPR/Cas-9-mediated deletion of exon 13 A sharply reduces the growth and metastasis of LH2b-expressing LUADs in mice. These findings identify a previously unrecognized collagen GGT activity that drives LUAD 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.