Affinage

LOXL2

Lysyl oxidase homolog 2 · UniProt Q9Y4K0

Length
774 aa
Mass
86.7 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LOXL2 is a copper-dependent lysyl oxidase-like amine oxidase that drives fibrosis, epithelial-to-mesenchymal transition (EMT), and metastasis through both catalytic and non-catalytic activities operating across extracellular, cytoplasmic, and nuclear compartments (PMID:10212285, PMID:19625348, PMID:28720577). Structurally it forms a rod-like molecule with scavenger-receptor cysteine-rich (SRCR) domains forming a stalk and the catalytic domain at the tip; it binds and deaminates tropoelastin to generate crosslinked elastin-like material (PMID:30676771), and is the principal isoform crosslinking and stabilizing insoluble collagen in tumor tissue, thereby activating focal-adhesion/FAK/SRC signaling in mesenchymal cells (PMID:27694892). Extracellularly, secreted LOXL2 remodels the matrix and the metastatic niche by activating stromal fibroblasts via integrin/FAK signaling (PMID:24008674), modulating TIMP-1/MMP9 (PMID:21233336), and—in cardiac and hepatic fibrosis—stimulating PI3K/AKT and TGF-β2 to drive myofibroblast transformation and collagen crosslinking (PMID:27966531, PMID:28073888). A central oncogenic axis is the stabilization and induction of the EMT transcription factor Snail1: LOXL2 attenuates GSK3β-dependent Snail1 degradation (PMID:16294032) and, when accumulated in the ER, binds HSPA5/GRP78 to activate IRE1-XBP1 signaling that transcriptionally induces SNAI1/SNAI2/ZEB2/TCF3 (PMID:28332555), repressing E-cadherin in cooperation with E47 (PMID:24632622). Several of these intracellular functions are independent of catalytic activity, as catalytically inactive mutants and the L2Δ13 isoform still repress E-cadherin, activate FAK/Src, and promote invasion (PMID:22157764, PMID:24414204, PMID:31911079). Catalytic activities include unconventional chemistry: oxidative deamination of trimethylated TAF10 to release it from TFIID-controlled promoters (PMID:25959397), deamination of H3K4me3 (H3K4ox) that organizes heterochromatin and restrains the DNA-damage response (PMID:27735137, PMID:31462706), and deacetylation of aldolase A at K13 to reprogram glycolysis (PMID:36209516). LOXL2 expression is itself controlled by hypoxia/HIF-1, ZEB1/miR-200, SMYD3, and Wnt signaling (PMID:20026874, PMID:27694892, PMID:26980013, PMID:32686768), and its protein and mRNA levels are tuned by TRIM44-mediated ubiquitination and RPS7-mediated mRNA stabilization (PMID:36512309, PMID:38326908). Genetic ablation studies indicate that in lung fibrosis LOXL2 is dispensable for pathological collagen crosslinking—LOXL4 being the critical isoform—while in mammary and pancreatic metastasis LOXL2 acts through ECM-independent niche-forming and Snail1-linked mechanisms (PMID:28720577, PMID:37235663, PMID:35428659).

Mechanistic history

Synthesis pass · year-by-year structured walk · 30 steps
  1. 1999 High

    Established LOXL2 as a distinct lysyl oxidase-family amine oxidase and raised the possibility of non-canonical processing/localization because its first exon lacks a signal sequence.

    Evidence cDNA cloning, gene structure analysis, in situ hybridization, and sequence homology

    PMID:10212285

    Open questions at the time
    • No functional substrate identified at this stage
    • Subcellular localization inferred from sequence, not measured
    • Catalytic activity not biochemically demonstrated
  2. 2005 Medium

    Connected LOXL2 to EMT by showing it stabilizes Snail1 against GSK3β-dependent degradation, providing a transcriptional route to E-cadherin repression.

    Evidence Co-immunoprecipitation and functional interaction assays linking LOXL2, GSK3β, and Snail1

    PMID:16294032

    Open questions at the time
    • Whether catalytic activity is required not addressed here
    • Single-lab interaction without reciprocal structural mapping
    • Mechanism of GSK3β attenuation unresolved
  3. 2009 High

    Resolved that LOXL2 acts in two compartments—secreted LOXL2 drives invasion via Src/FAK while intracellular LOXL2 engages the Snail/E-cadherin pathway—and showed antibody blockade of secreted LOXL2 is therapeutically tractable.

    Evidence RNAi, overexpression, Src/FAK western blot, xenografts, and anti-LOXL2 antibody in gastric cancer

    PMID:19625348

    Open questions at the time
    • Molecular target of secreted LOXL2 on the cell surface not defined
    • Catalytic dependence of each compartmental activity untested
  4. 2009 High

    Placed LOXL2 downstream of hypoxia by identifying it as a direct HIF-1 target necessary and sufficient for hypoxic E-cadherin repression and invasion.

    Evidence HIF-1 binding analysis, gain/loss-of-function, and invasion assays under hypoxia

    PMID:20026874

    Open questions at the time
    • Mechanism linking LOXL2 to E-cadherin repression under hypoxia not dissected here
    • Relative contribution of LOX vs LOXL2 not separated
  5. 2010 Medium

    Extended LOXL2 function to normal development, showing it is the major chondrocyte lysyl oxidase required for differentiation via SNAIL/SOX9 regulation.

    Evidence LOX-isoform expression profiling in fracture healing and LOXL2 knockdown in ATDC5 cells

    PMID:21071451

    Open questions at the time
    • Catalytic requirement not tested
    • In vivo developmental phenotype not established here
  6. 2011 High

    Demonstrated that LOXL2's pro-invasive and differentiation-suppressing activities can be catalytic-independent, mapping a non-enzymatic function to the fourth SRCR domain.

    Evidence Catalytically inactive Y689F and domain-deletion mutants, BAPN inhibitor, AB0023 antibody, and involucrin/TIMP1/MMP9 readouts

    PMID:21233336 PMID:22157764

    Open questions at the time
    • Molecular partners of the SRCR domain not identified at this stage
    • How a non-catalytic LOXL2 modulates MMP9/TIMP1 not mechanistically defined
  7. 2011 Medium

    Showed cytoplasmic/perinuclear LOXL2 actively maintains the mesenchymal state by repressing polarity and tight-junction genes (Lgl2, claudin-1), with silencing reverting cells toward an epithelial phenotype.

    Evidence LOXL2 silencing, gene expression, polarity/tight-junction immunofluorescence, and tumorigenicity assays in basal-like breast cells

    PMID:21732535

    Open questions at the time
    • Direct vs indirect transcriptional control of Lgl2/claudin-1 unresolved
    • Nuclear targeting mechanism not defined
  8. 2013 High

    Defined LOXL2 as a tumor-stroma signal: secreted LOXL2 activates fibroblasts through integrin/FAK and, through ROS, activates ErbB2 to disrupt epithelial morphogenesis.

    Evidence Recombinant LOXL2 on collagen matrices, FAK phosphorylation, α-SMA staining, 3D acinar cultures, ROS/ErbB2 analysis with pharmacologic rescue

    PMID:23971878 PMID:24008674

    Open questions at the time
    • Integrin receptor identity engaged by LOXL2 not pinned down
    • Source of ROS (catalytic byproduct vs indirect) not defined here
  9. 2014 High

    Consolidated the non-catalytic, partner-dependent transcriptional role of LOXL2, showing inactive mutants cooperate with Snail1 and E47 to repress E-cadherin and that LOXL2 directly programs metastatic-niche cytokines.

    Evidence Catalytic-mutant overexpression, reciprocal Co-IP with E47, E-cadherin promoter luciferase, FAK/Src blots, and in vivo lung metastasis/BMDC recruitment assays

    PMID:24414204 PMID:24632622

    Open questions at the time
    • Stoichiometry/architecture of LOXL2–E47 transcriptional complex unknown
    • Direct vs cofactor role at cytokine promoters not fully separated
  10. 2014 Medium

    Broadened the cytoplasmic interactome and downstream signaling, linking LOXL2 to integrin turnover, MARCKSL1-dependent survival signaling, and an enzymatically impaired splice isoform with distinct pro-invasive wiring.

    Evidence Co-IP/domain mapping (MARCKSL1, SRCR), protease/proteasome inhibitor experiments on integrins, FAK/Akt/mTOR blots, and Δe13 isoform MAPK8-dependent rescue

    PMID:24863880 PMID:25092917 PMID:25275797

    Open questions at the time
    • Single-lab Co-IPs without structural validation
    • How LOXL2 controls integrin proteolysis mechanistically unclear
    • Generality of Δe13 isoform across tumors untested
  11. 2016 High

    Revealed an unconventional catalytic biology in which recombinant LOXL2 deaminates H3K4me3, providing a chemical mechanism for histone modification tied to CDH1 transcription.

    Evidence In vitro deamination with recombinant LOXL2, infrared spectroscopy, mass spectrometry, and CDH1 transcription analysis

    PMID:27735137

    Open questions at the time
    • Genome-wide distribution of the mark not yet mapped here
    • Reader/effector of H3K4ox unidentified at this stage
  12. 2015 High

    Identified a non-histone nuclear substrate, showing LOXL2 oxidizes methylated TAF10 to evict it from TFIID-dependent promoters, with developmental consequences for pluripotency and neural differentiation.

    Evidence Unbiased proteomic substrate ID, in vitro oxidation, ChIP-seq, ES-cell pluripotency analysis, and zebrafish loss-of-function

    PMID:25959397

    Open questions at the time
    • Breadth of methylated protein substrates beyond TAF10 unknown
    • How nuclear LOXL2 is targeted to specific promoters not defined
  13. 2016 High

    Established upstream control of LOXL2 by the ZEB1/miR-200 EMT axis and confirmed LOXL2 as the principal collagen-crosslinking isoform that feeds back into FAK/SRC signaling during metastasis.

    Evidence miR-200/ZEB1 gain/loss-of-function, collagen solubility assays, FAK/SRC blots, and in vivo metastasis; SMYD3 ChIP identifying direct promoter binding

    PMID:26980013 PMID:27694892

    Open questions at the time
    • Whether crosslinking and signaling effects are separable not resolved
    • Tissue-context dependence of these regulators not mapped
  14. 2016 High

    Demonstrated LOXL2's pathogenic role in cardiac fibrosis, with secreted LOXL2 stimulating fibroblasts through PI3K/AKT to produce TGF-β2 and drive myofibroblast transformation.

    Evidence Genetic Loxl2 disruption and antibody inhibition in mice, PI3K/AKT-TGF-β2 pathway analysis, cardiac function and fibrosis quantification with human-sample replication

    PMID:27966531

    Open questions at the time
    • Receptor mediating LOXL2-to-fibroblast signaling not identified
    • Catalytic dependence of the cardiac effect not tested
  15. 2017 High

    Defined an ER-stress route to EMT, in which accumulated LOXL2 binds HSPA5/GRP78 to activate IRE1-XBP1, which transcriptionally induces multiple EMT transcription factors.

    Evidence Reciprocal Co-IP, ER fractionation, IRE1/XBP1 pathway analysis, XBP1 ChIP at EMT-TF promoters, and IRE1 inhibitor rescue

    PMID:28332555

    Open questions at the time
    • What triggers ER accumulation of LOXL2 unclear
    • Catalytic requirement of HSPA5 engagement untested
  16. 2017 High

    Distinguished LOXL2's metastasis-promoting function from canonical ECM crosslinking using conditional models in breast and showed a parallel ECM-crosslinking role in liver fibrosis and progenitor-cell fate.

    Evidence Conditional PyMT ablation/overexpression with ECM stiffness measurement; anti-LOXL2 antibody across TAA/Mdr2/DDC liver models with crosslinking assays and EpCAM+ HPC differentiation

    PMID:28073888 PMID:28720577

    Open questions at the time
    • Mechanism of ECM-independent metastatic function not fully resolved
    • Whether liver and breast functions share effectors unknown
  17. 2018 High

    Closed a mechanotransduction loop in which matrix stiffness induces LOXL2 via integrin β1/β5→JNK/c-JUN, and secreted LOXL2 builds the pre-metastatic niche through MMP9, fibronectin, CXCL12, and BMDC recruitment.

    Evidence Tunable-stiffness substrates, integrin shRNA, JNK inhibitor, c-JUN knockdown, conditioned-medium experiments, and effector quantification in HCC

    PMID:29728125

    Open questions at the time
    • Direct vs indirect transcriptional control of niche factors not separated
    • Single-lab characterization
  18. 2019 High

    Provided the structural basis for LOXL2 architecture and demonstrated direct tropoelastin binding and deamination producing elastin-like crosslinked material, defining a bona fide ECM crosslinking substrate.

    Evidence X-ray scattering, electron microscopy, binding assay, in vitro deamination, and proteomic identification of crosslinked peptides

    PMID:30676771

    Open questions at the time
    • High-resolution catalytic-site structure not obtained
    • In vivo elastin crosslinking by LOXL2 not demonstrated here
  19. 2019 Medium

    Linked LOXL2 to cytoskeletal control by identifying actin-binding partners (ezrin, fascin, HSPB1, TMOD3, vimentin) and showing PKCα-dependent ezrin T567 phosphorylation drives invasion, including catalytic-independent metastasis.

    Evidence MS interactome with Co-IP validation, ezrin phosphorylation blots, PKCα inhibitor, vimentin pull-down/MS, and in vivo metastasis with catalytic-inactive mutants

    PMID:31409639 PMID:31911079

    Open questions at the time
    • Direct vs indirect role of LOXL2 in ezrin phosphorylation unclear
    • Whether vimentin interaction is functionally required not established
  20. 2019 Medium

    Added a transcription-promoting partnership in which LOXL2 binds GATA6 via its SRCR domain to upregulate VEGFA and angiogenesis in cholangiocarcinoma.

    Evidence Co-IP, SRCR-domain mapping, VEGFA qRT-PCR/ELISA, tube formation, and in vivo tumor growth

    PMID:31322171

    Open questions at the time
    • Single Co-IP-based interaction without structural validation
    • Direct LOXL2 action at VEGFA locus not shown
  21. 2019 High

    Mapped genome-wide H3K4ox to heterochromatin in triple-negative breast cancer and showed LOXL2 loss decompacts chromatin and sustains DNA-damage signaling, sensitizing cells to therapy.

    Evidence H3K4ox ChIP-seq, chromatin accessibility assays, DDR markers, drug-sensitivity, and PDX models

    PMID:31462706

    Open questions at the time
    • Mechanism targeting LOXL2 to heterochromatin unknown
    • Reader of H3K4ox still unidentified
  22. 2020 Medium

    Connected LOXL2 to glycolytic reprogramming via a catalysis-dependent Snail-FBP1 axis that elevates HIF-1α/VEGF signaling, distinguishing intracellular from extracellular function.

    Evidence Overexpression/silencing, Y689F catalytic mutant, anti-LOXL2 antibody, FBP1 knockdown, and HIF-1α/VEGF readouts with LOXL2-IN-1 in HCC

    PMID:32323822

    Open questions at the time
    • Direct enzymatic step in the Snail-FBP1 axis not pinpointed
    • Single-lab study
  23. 2020 High

    Identified upstream Wnt control of LOXL2 in osteosarcoma and a TGF-β1-driven nuclear LOXL2 requirement for myofibroblast differentiation, reinforcing both transcriptional regulation and a nuclear Snail-linked fibrotic role.

    Evidence GEMMs with c-Fos ChIP and Wls inactivation, BAPN/shRNA/antibody inhibition for osteosarcoma; nuclear LOXL2 fractionation, TGF-β1 treatment, and siRNA silencing in lung fibroblasts

    PMID:32686768 PMID:33248114

    Open questions at the time
    • How nuclear LOXL2 controls Snail in fibroblasts not mechanistically defined
    • Catalytic dependence of nuclear fibrotic function untested
  24. 2021 High

    Established LOXL2 as a redox driver of the Warburg effect, generating hydrogen peroxide that stabilizes HIF-1α against PHD hydroxylation in a feedforward loop, and linked LOXL2 induction to macrophage-derived OSM in pancreatic cancer.

    Evidence Overexpression/knockdown with HIF-1α stability and H2O2 assays and metabolic flux in PDAC; conditional GEMMs (KPC/KCL2KO/KCL2KI) with OSM treatment, macrophage depletion, and ECM/metastasis analysis

    PMID:34836938 PMID:35428659

    Open questions at the time
    • Whether H2O2 production is the catalytic byproduct of substrate oxidation not directly shown
    • Coupling between redox and ECM functions unclear
  25. 2021 Medium

    Reinforced the Snail-driven, non-ECM-crosslinking oncogenic outputs of LOXL2 by showing it promotes vasculogenic mimicry through SNAIL upregulation in HCC.

    Evidence Gain/loss-of-function, tube formation, SNAIL blots, xenografts, and CD31/PAS staining in patient samples

    PMID:30506621

    Open questions at the time
    • Catalytic requirement not tested
    • Single-lab study
  26. 2022 High

    Uncovered a moonlighting deacetylase activity, showing LOXL2 (and L2Δ13) deacetylates aldolase A at K13 to mobilize it from actin and enhance glycolysis, broadening LOXL2's catalytic repertoire beyond amine oxidation.

    Evidence SILAC proteomics, in vitro deacetylation, K13-acetylation antibody, aldolase activity/fractionation, and knock-in mouse metabolomics/transcriptomics in esophageal cancer

    PMID:36209516

    Open questions at the time
    • Catalytic mechanism for deacetylation by an amine oxidase fold unresolved
    • Substrate scope of LOXL2 deacetylase activity unknown
  27. 2022 Medium

    Defined post-translational control of LOXL2 levels by TRIM44-mediated ubiquitination, linking LOXL2 stability to ECM remodeling and antitumor immunity in gastric cancer.

    Evidence Co-IP, co-localization, ubiquitination assay, and in vivo tumor immunity assays

    PMID:36512309

    Open questions at the time
    • Whether TRIM44 stabilizes or destabilizes LOXL2 ubiquitin chains needs clarification
    • Single-lab interaction
  28. 2023 Medium

    Showed LOXL2 functions within a LOXL2-MMP9-LCN2 ternary complex with compartment-specific assembly that drives matrix degradation, filopodia formation, and FAK/AKT/GSK3β signaling.

    Evidence Compartment-resolved Co-IP, migration/invasion assays, filopodia imaging, profilin-1 analysis, signaling blots, and in vivo tumor growth

    PMID:37753805

    Open questions at the time
    • Direct vs bridged interactions within the ternary complex not fully resolved
    • Single-lab characterization
  29. 2023 High

    Refined isoform specificity in fibrosis by showing that, in lung, LOXL4—not LOXL2—is the critical determinant of pathological collagen crosslinking, with LOXL2 ablation giving only modest effects.

    Evidence Single and double Loxl2/Loxl4 knockouts in pulmonary fibrosis with crosslinking biochemistry and fibrosis quantification

    PMID:37235663

    Open questions at the time
    • Whether LOXL2 contributes to non-crosslinking fibrotic functions in lung not addressed
    • Tissue-specific division of labor among LOX isoforms incompletely mapped
  30. 2024 High

    Added mRNA-level control, showing RPS7 binds AUUUA motifs in the LOXL2 3'UTR to stabilize its transcript, raising LOXL2 protein that sustains ITGB1 and activates ITGB1/FAK/SRC signaling in HCC metastasis.

    Evidence RIP, RNA-pulldown, luciferase, mRNA-decay and nascent-RNA assays, ITGB1 stability assays, FAK/SRC blots, and in vivo metastasis

    PMID:38326908

    Open questions at the time
    • Whether RPS7 control of LOXL2 operates broadly across tissues unknown
    • Mechanism by which LOXL2 stabilizes ITGB1 protein not detailed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LOXL2's multiple catalytic activities (amine oxidation of ECM substrates, deamination of TAF10/H3K4me3, and deacetylation of aldolase A) and its catalytic-independent scaffolding functions are partitioned across subcellular compartments, and what governs its localization to ER, nucleus, cytoskeleton, and extracellular space, remains unresolved.
  • No unified model for compartmental targeting of LOXL2
  • Structural basis for how one fold catalyzes oxidation and deacetylation undefined
  • Which functions are therapeutically separable by enzyme inhibition vs antibody blockade unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 5 GO:0140096 catalytic activity, acting on a protein 3 GO:0140110 transcription regulator activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0042393 histone binding 2
Localization
GO:0005576 extracellular region 3 GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0031012 extracellular matrix 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1474244 Extracellular matrix organization 4 R-HSA-1643685 Disease 4 R-HSA-1430728 Metabolism 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1266738 Developmental Biology 2
Partners
E47 (TCF3)EZRGATA6HSPA5MMP9SNAI1TRIM44VIM
Complex memberships
LOXL2-MMP9-LCN2 ternary complex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 LOXL2 encodes a new lysyl oxidase-like amine oxidase with conserved copper-binding and catalytic domains; unlike LOX and LOXL, exon 1 of LOXL2 does not encode a signal sequence, suggesting different processing and intracellular localization. The protein has four divergent N-terminal exons and five conserved C-terminal exons encoding the catalytic domain. cDNA cloning, gene structure analysis, in situ hybridization, sequence homology analysis The Journal of biological chemistry High 10212285
2005 LOXL2 physically interacts with and functionally stabilizes the EMT transcription factor Snail1 by attenuating GSK3β-dependent phosphorylation and subsequent ubiquitination/degradation of Snail1, thereby promoting E-cadherin repression and EMT. Co-immunoprecipitation, functional interaction assays, discussion of epistasis between LOXL2 and GSK3β in Snail regulation Cell cycle (Georgetown, Tex.) Medium 16294032
2009 Secreted extracellular LOXL2 promotes gastric cancer invasion and metastasis via the Src/FAK signaling pathway, whereas intracellular LOXL2 also activates the Snail/E-cadherin pathway; antibody blockade of secreted LOXL2 inhibits tumor growth and metastasis. RNA interference knockdown, ectopic overexpression, Src/FAK western blot, in vivo xenograft, anti-LOXL2 antibody treatment Carcinogenesis High 19625348
2009 LOX and LOXL2 are direct transcriptional targets of HIF-1 under hypoxia; their activation is necessary and sufficient for hypoxic repression of E-cadherin, mediating epithelial-to-mesenchymal transition and cellular invasion. HIF-1 transcription factor binding analysis, gene expression assays, cellular invasion assays, gain/loss-of-function experiments under hypoxic conditions The Journal of biological chemistry High 20026874
2010 LOXL2 is the major lysyl oxidase isoform expressed in chondrocytes during fracture healing; LOXL2 knockdown in ATDC5 chondrogenic cells impairs differentiation by altering expression of SNAIL and SOX9, demonstrating LOXL2 is required for chondrocyte differentiation. Expression profiling of LOX isoforms in fracture healing, in vitro LOXL2 knockdown in chondrogenic cell line, gene expression analysis of SNAIL and SOX9 The Journal of biological chemistry Medium 21071451
2011 LOXL2 promotes breast cancer invasion by regulating expression and activity of TIMP-1 and MMP9 in the extracellular environment; genetic, chemical, or antibody-mediated inhibition of LOXL2 reduces metastasis in orthotopic and transgenic models. Genetic knockdown, chemical inhibition, antibody inhibition, in vivo orthotopic and transgenic breast cancer models, protein expression analysis of TIMP1/MMP9 Cancer research High 21233336
2011 Cytoplasmic/perinuclear LOXL2 maintains mesenchymal phenotype in basal-like breast carcinoma cells through transcriptional downregulation of Lgl2 and claudin-1, causing disorganization of cell polarity and tight junction complexes; LOXL2 silencing induces mesenchymal-to-epithelial transition. LOXL2 silencing, gene expression analysis, immunofluorescence of polarity/tight junction markers, in vivo tumorigenicity assay EMBO molecular medicine Medium 21732535
2011 LOXL2 inhibition in enzymatic activity assays using catalytically inactive mutants (LOXL2 Y689F) and deletion of catalytic domain still inhibits keratinocyte differentiation, demonstrating the enzymatic activity of LOXL2 is not required for inhibition of keratinocyte differentiation; this activity requires the fourth SRCR domain. Catalytically inactive point mutant (Y689F), catalytic domain deletion mutant, β-aminopropionitrile enzymatic inhibitor, AB0023 function-blocking antibody, involucrin expression as differentiation readout The Journal of biological chemistry High 22157764
2013 Tumor-secreted LOXL2 activates stromal fibroblasts through integrin-mediated focal adhesion kinase (FAK) activation, inducing α-SMA expression, fibroblast branching on collagen matrices, collagen contraction, and fibroblast invasion. In vitro fibroblast activation assays on collagen matrices, recombinant LOXL2 treatment, FAK phosphorylation western blot, α-SMA immunostaining, in vivo orthotopic tumor models with LOXL2 manipulation Molecular cancer research : MCR High 24008674
2013 LOXL2 induces aberrant acinar morphogenesis in normal mammary epithelial cells through production of reactive oxygen species (ROS) that activates ErbB2; ErbB2 inhibition (Herceptin, lapatinib) abrogates LOXL2-induced abnormal proliferation, disrupted polarity and lumen formation. LOXL2 overexpression in MCF10A 3D acinar cultures, ROS measurement, ErbB2 phosphorylation analysis, pharmacological ErbB2 inhibition, invasion assays Breast cancer research : BCR Medium 23971878
2014 Catalytically inactive LOXL2 mutants collaborate with Snail1 in E-cadherin gene repression and promote FAK/Src pathway activation to trigger EMT, demonstrating a non-catalytic role of LOXL2 in regulating epithelial cell plasticity. Catalytically inactive LOXL2 mutant overexpression, E-cadherin promoter activity assays, FAK/Src phosphorylation western blot, EMT marker analysis Biology open Medium 24414204
2014 LOXL2 interacts with the bHLH transcription factor E47 and functionally collaborates in repression of the E-cadherin promoter; LOXL2 and E47 together regulate recruitment of bone marrow progenitor cells to lungs and directly transcriptionally regulate fibronectin and cytokines TNFα, ANG-1 and GM-CSF during metastatic colonization. Co-immunoprecipitation, E-cadherin promoter luciferase assay, loss/gain-of-function in syngeneic breast cancer models, in vivo lung metastasis assay, bone marrow progenitor cell recruitment assay Oncogene High 24632622
2014 LOXL2 regulates integrin α5 and integrin β1 protein levels via protease- and proteasome-dependent degradation systems, promoting stress fiber and focal adhesion formation in renal clear cell carcinoma cells. RNAi knockdown, protease/proteasome inhibitor experiments, integrin α5/β1 western blot, stress fiber and focal adhesion imaging Molecular cancer research : MCR Medium 25092917
2014 LOXL2 interacts with MARCKSL1 through its scavenger receptor domain (interacting with the N-terminal domain of MARCKSL1); LOXL2 activates FAK/Akt/mTOR signaling pathways and inhibits MARCKSL1-induced apoptosis, promoting cell proliferation. Co-immunoprecipitation, domain mapping, luciferase reporter assay, cell cycle and apoptosis analysis, FAK/Akt/mTOR phosphorylation western blot Cellular signalling Medium 24863880
2014 LOXL2 alternative splicing isoform LOXL2 Δe13, lacking exon 13, shows impaired deamination enzymatic activity but promotes cell migration and invasion of esophageal squamous cell carcinoma cells to greater degrees than full-length LOXL2, operating through MAPK8 rather than FAK/AKT/ERK pathways. Isoform identification and cloning, enzymatic deamination assay, gene expression profiling, MAPK8 knockdown rescue experiment, migration/invasion assays Biochemistry and cell biology Medium 25275797
2015 LOXL2 oxidizes methylated TAF10 (a TFIID complex member), causing its release from promoters and blocking TFIID-dependent gene transcription; in embryonic stem cells this inactivates pluripotency genes, and in zebrafish loss of LOXL2 causes aberrant Sox2 overexpression and impaired neural differentiation. Unbiased proteomic substrate identification, in vitro oxidation assay, ChIP-seq, embryonic stem cell pluripotency gene analysis, zebrafish LOXL2 loss-of-function Molecular cell High 25959397
2016 Recombinant LOXL2 specifically deaminates trimethylated lysine 4 on histone H3 (H3K4me3), as shown by infrared spectroscopy and mass spectrometry; this LOXL2-catalyzed H3K4 deamination is linked to transcriptional control of the CDH1 (E-cadherin) gene, representing a novel unconventional chemical mechanism for histone modification. In vitro deamination assay with recombinant LOXL2, infrared spectroscopy, mass spectrometry, CDH1 transcription analysis The FEBS journal High 27735137
2016 LOXL2 expression in metastatic lung cancer cells is directly regulated by ZEB1 (transcriptional activator) and repressed by the miR-200 family; LOXL2, as opposed to LOX, is the principal isoform crosslinking and stabilizing insoluble collagen deposition in tumor tissues, which activates focal adhesion/FAK/SRC signaling in mesenchymal tumor cells. miR-200/ZEB1 gain/loss-of-function, collagen solubility assay, FAK/SRC phosphorylation western blot, in vivo metastasis models Oncogene High 27694892
2016 In cardiac stress, LOXL2 secreted by activated fibroblasts into the interstitium promotes cardiac fibrosis by stimulating fibroblasts through PI3K/AKT signaling to produce TGF-β2, promoting fibroblast-to-myofibroblast transformation; LOXL2 also acts downstream of TGF-β2 to stimulate myofibroblast migration. Genetic Loxl2 disruption in mice, antibody-mediated inhibition, PI3K/AKT and TGF-β2 pathway analysis, cardiac function assessment, fibrosis quantification Nature communications High 27966531
2016 SMYD3 methyltransferase directly binds the promoter regions of EZR and LOXL2 and stimulates their transcription in esophageal squamous cell carcinoma, as demonstrated by chromatin immunoprecipitation assay. Chromatin immunoprecipitation (ChIP) assay, RNAi knockdown, immunohistochemistry correlation analysis Human pathology Medium 26980013
2017 LOXL2 overexpression accumulates in the endoplasmic reticulum where it interacts with HSPA5 (GRP78), leading to activation of the IRE1-XBP1 arm of the ER stress response; XBP1 then directly transcriptionally activates EMT transcription factors SNAI1, SNAI2, ZEB2, and TCF3; IRE1 inhibition blocks LOXL2-dependent EMT. Co-immunoprecipitation, ER fractionation, IRE1/XBP1 pathway analysis, ChIP for XBP1 at EMT-TF promoters, IRE1 pharmacological inhibition rescue experiment Scientific reports High 28332555
2017 LOXL2 mediates collagen crosslinking in fibrotic liver septa and promotes hepatic progenitor cell (HPC) differentiation towards ductal/fibrogenic fate; anti-LOXL2 antibody reduces collagen crosslinking, suppresses bridging fibrosis progression, and promotes fibrosis reversal; LOXL2 blockade in vitro directly shifts primary EpCAM+ HPC differentiation towards hepatocytes away from ductal lineage. Anti-LOXL2 monoclonal antibody treatment in multiple mouse fibrosis models (TAA, Mdr2-/-, DDC), collagen crosslinking biochemical assay, morphometric collagen quantification, primary EpCAM+ cell in vitro differentiation assay Gut High 28073888
2017 LOXL2 ablation in conditional transgenic mouse models dramatically decreases lung metastasis without affecting primary tumor ECM stiffness or organization, indicating a function independent of conventional ECM crosslinking; LOXL2 action is associated with elevated Snail1 levels and expression of cytokines promoting premetastatic niche formation. Conditional transgenic PyMT mouse models with LOXL2 ablation or overexpression, ECM stiffness measurement, Snail1 and cytokine expression analysis Cancer research High 28720577
2018 Higher matrix stiffness upregulates LOXL2 expression in HCC cells through the integrin β1/α5 → JNK/c-JUN signaling pathway; secreted LOXL2 promotes pre-metastatic niche formation by upregulating MMP9 and fibronectin production in lung fibroblasts via Akt pathway activation, and increasing CXCL12 expression and BMDC recruitment. Gel-based stiffness substrate system, integrin shRNA knockdown, JNK inhibitor treatment, shRNA-c-JUN knockdown, conditioned medium experiments, MMP9/fibronectin/CXCL12 western blot/ELISA Journal of experimental & clinical cancer research : CR High 29728125
2019 Full-length LOXL2 has a rod-like structure with SRCR domains forming a stalk and the catalytic domain at the tip; LOXL2 directly binds tropoelastin and catalyzes its deamination to form crosslinked elastin-like material resistant to trypsin proteolysis with mechanical properties similar to mature elastin; specific allysine-containing cross-linked peptides were identified by proteomics. X-ray scattering, electron microscopy (low-resolution structure), surface plasmon resonance or equivalent binding assay, in vitro deamination assay, proteomics identification of crosslinked peptides FASEB journal High 30676771
2019 LOXL2 and its catalytically inactive isoform L2Δ13 interact physically with actin-binding proteins ezrin (EZR), fascin (FSCN1), HSPB1, and TMOD3 in the cytoplasm; LOXL2 promotes phosphorylation of ezrin at T567 (requiring PKCα co-activity), which is critical for cytoskeletal reorganization and tumor cell invasion in esophageal squamous cell carcinoma. Interactome analysis (mass spectrometry), Co-IP validation, ezrin T567 phosphorylation western blot after LOXL2 depletion/re-expression, PKCα inhibitor experiment, in vivo tumor progression assay Cancer research High 31409639
2019 LOXL2 interacts physically with GATA6 via its scavenger receptor cysteine-rich domain; the LOXL2/GATA6 complex regulates VEGFA mRNA expression and protein secretion, promoting angiogenesis in cholangiocarcinoma. Co-immunoprecipitation, domain mapping (SRCR domain), qRT-PCR and ELISA for VEGFA, tube formation assay, in vivo tumor growth assay International journal of oncology Medium 31322171
2019 LOXL2-mediated H3K4ox (oxidation of H3K4me3) is elevated in triple-negative breast cancer and is located primarily in heterochromatin; LOXL2 knockdown reduces H3K4ox, causing chromatin decompaction and sustained DNA damage response activation, increasing susceptibility to anticancer agents. ChIP-seq for H3K4ox, LOXL2 knockdown, ATAC-seq or chromatin accessibility assay, DNA damage response markers, drug sensitivity assays, patient-derived xenograft models Oncogene High 31462706
2020 Wnt signaling (via Wnt7b and Wnt9a, regulated by c-Fos/AP-1) promotes Loxl2 expression through transcription factors Zeb1 and Zeb2 in osteosarcoma; Loxl2 inhibition reduces osteosarcoma cell proliferation and decreases tumor growth and lung colonization in murine and human orthotopic models. Genetically modified mouse models (GEMMs), c-Fos promoter binding (ChIP), Wls gene inactivation, BAPN and specific Loxl2 shRNA/antibody inhibition, in vitro and in vivo proliferation and tumor assays Cell research High 32686768
2019 LOXL4 (not LOXL2) is the critical determinant of pathological collagen crosslinking and fibrosis in the lung; genetic ablation of LOXL2 alone leads to only modest reduction in pathological collagen crosslinking without reducing fibrosis, while LOXL4 deletion markedly disrupts both; double knockout offers no additive effect over LOXL4 deletion alone. Genetic knockout of Loxl2 and/or Loxl4 in mouse pulmonary fibrosis model, collagen crosslinking biochemical assay, fibrosis quantification Science advances High 37235663
2020 LOXL2 upregulates HIF-1α signaling through the Snail-FBP1 axis in hepatocellular carcinoma: intracellular LOXL2 (requiring enzymatic activity, as the Y689F mutant lacks this effect) upregulates Snail, which represses FBP1, thereby enhancing glycolysis and HIF-1α/VEGF signaling; extracellular LOXL2 blockade by antibody does not abrogate this intracellular pathway. LOXL2 overexpression/silencing, LOXL2 Y689F catalytic mutant, anti-LOXL2 antibody, FBP1 knockdown, Snail western blot, HIF-1α/VEGF expression, LOXL2-IN-1 small molecule inhibitor Oncology reports Medium 32323822
2020 Nuclear LOXL2 in lung fibroblasts is upregulated by TGF-β1 treatment and is required for TGF-β1-induced proto-myofibroblast appearance and myofibroblast differentiation; LOXL2 silencing abrogates TGF-β1-induced nuclear Snail upregulation and myofibroblast evolution. Nuclear LOXL2 fractionation/immunostaining in vivo (ARDS model), TGF-β1 treatment of lung fibroblasts, LOXL2 siRNA silencing, Snail and myofibroblast marker expression European journal of pharmacology Medium 33248114
2021 LOXL2 stabilizes HIF-1α from prolyl hydroxylase (PHD)-dependent hydroxylation via hydrogen peroxide generation, creating a positive feedback loop that facilitates transcription of glycolytic genes and the Warburg effect in pancreatic ductal adenocarcinoma. LOXL2 overexpression/knockdown, HIF-1α stability assay (PHD inhibitor comparison), H2O2 measurement, glycolytic gene expression, metabolic flux analysis Cell death & disease Medium 34836938
2021 Tumor-associated macrophage-secreted oncostatin M (OSM) induces LOXL2 expression in pancreatic cancer cells; Loxl2 loss in PDAC mouse models significantly decreases metastasis through non-cell-autonomous ECM remodeling effects; targeting macrophages in vivo reduces Osm and Loxl2 expression and collagen fiber alignment. Conditional GEMM (KPC/KCL2KO and KCL2KI mice), OSM treatment and macrophage depletion in vivo, ECM collagen fiber alignment analysis, metastasis quantification, overall survival analysis Gut High 35428659
2021 LOXL2 promotes SNAIL expression to enable vasculogenic mimicry formation in hepatocellular carcinoma; LOXL2 overexpression significantly promotes migration, invasion, and tube formation in HCC cells. LOXL2 gain/loss-of-function in HCC cell lines, tube formation assay, SNAIL western blot, in vivo xenograft, CD31/PAS double staining in patient samples Journal of cellular and molecular medicine Medium 30506621
2022 LOXL2 and its catalytically inactive L2Δ13 isoform function as novel deacetylases: they directly catalyze deacetylation of aldolase A at K13, stimulating aldolase mobilization from the actin cytoskeleton, enhancing glycolytic activity, and promoting metabolic reprogramming and tumor progression in esophageal cancer. SILAC proteomics, in vitro deacetylation assay, aldolase A K13 acetylation-specific antibody, aldolase activity assay, actin cytoskeleton fractionation, knock-in mouse model metabolomics/transcriptomics Redox biology High 36209516
2022 TRIM44 directly binds LOXL2 and regulates its protein stability via ubiquitination; TRIM44-mediated LOXL2 stabilization promotes ECM remodeling that modulates T-cell-mediated antitumor immunity in gastric cancer. Co-immunoprecipitation, immunofluorescence co-localization, ubiquitination assay, in vivo tumor immunity assay Cellular oncology (Dordrecht, Netherlands) Medium 36512309
2022 LOXL2 in rhabdomyosarcoma promotes cell migration, invasion, and lung metastasis independently of catalytic activity; vimentin was identified as a LOXL2-interacting cytoskeletal protein by pull-down/mass spectrometry, suggesting regulation of cytoskeleton dynamics as the mechanism. Stable LOXL2 knockdown, wild-type and catalytically inactive LOXL2 overexpression, in vivo metastasis assay, pull-down assay with mass spectrometry, vimentin validation Cancer letters Medium 31911079
2023 LOXL2, MMP9, and LCN2 form a ternary protein complex; LCN2-LOXL2 and LCN2-MMP9 interactions occur both intracellularly and extracellularly, while LOXL2-MMP9 interactions only occur intracellularly; the complex promotes fibronectin and Matrigel degradation, filopodia formation, microfilament rearrangement via profilin 1 upregulation, and activates FAK/AKT/GSK3β signaling. Co-immunoprecipitation (intracellular and extracellular fractions), cell migration/invasion assays, filopodia imaging, signaling pathway western blot, in vivo tumor growth assay Molecular oncology Medium 37753805
2024 RPS7 stabilizes LOXL2 mRNA by binding to AUUUA motifs in the 3155–3375 region of the LOXL2 3'UTR, increasing LOXL2 mRNA abundance; elevated LOXL2 then maintains ITGB1 protein stability and activates ITGB1-mediated FAK/SRC signaling, promoting HCC metastasis. RNA-binding protein immunoprecipitation (RIP), RNA-pulldown, dual luciferase reporter assay, LOXL2 mRNA decay assay, nascent RNA capture, ITGB1 protein stability assay, FAK/SRC phosphorylation western blot, in vivo lung metastasis model Journal of experimental & clinical cancer research : CR High 38326908

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Selective targeting of lysyl oxidase-like 2 (LOXL2) suppresses hepatic fibrosis progression and accelerates its reversal. Gut 229 28073888
2009 The lysyl oxidases LOX and LOXL2 are necessary and sufficient to repress E-cadherin in hypoxia: insights into cellular transformation processes mediated by HIF-1. The Journal of biological chemistry 218 20026874
2011 LOXL2-mediated matrix remodeling in metastasis and mammary gland involution. Cancer research 212 21233336
2016 Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment. Nature communications 208 27966531
2017 HIF-1α promoted vasculogenic mimicry formation in hepatocellular carcinoma through LOXL2 up-regulation in hypoxic tumor microenvironment. Journal of experimental & clinical cancer research : CR 183 28449718
2016 ZEB1 induces LOXL2-mediated collagen stabilization and deposition in the extracellular matrix to drive lung cancer invasion and metastasis. Oncogene 183 27694892
2009 Secreted LOXL2 is a novel therapeutic target that promotes gastric cancer metastasis via the Src/FAK pathway. Carcinogenesis 158 19625348
2011 Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas. EMBO molecular medicine 134 21732535
2017 Lysyl Oxidase-like Protein LOXL2 Promotes Lung Metastasis of Breast Cancer. Cancer research 126 28720577
2018 Matrix stiffness-upregulated LOXL2 promotes fibronectin production, MMP9 and CXCL12 expression and BMDCs recruitment to assist pre-metastatic niche formation. Journal of experimental & clinical cancer research : CR 119 29728125
2020 Wnt signaling and Loxl2 promote aggressive osteosarcoma. Cell research 100 32686768
2020 LOXL2 in cancer: regulation, downstream effectors and novel roles. Biochimica et biophysica acta. Reviews on cancer 97 32976981
2017 LOXL2 drives epithelial-mesenchymal transition via activation of IRE1-XBP1 signalling pathway. Scientific reports 95 28332555
2015 LOXL2 Is Highly Expressed in Cancer-Associated Fibroblasts and Associates to Poor Colon Cancer Survival. Clinical cancer research : an official journal of the American Association for Cancer Research 89 26206869
2021 LOXL2 Inhibitors and Breast Cancer Progression. Antioxidants (Basel, Switzerland) 87 33669630
2013 Tumor-secreted LOXL2 activates fibroblasts through FAK signaling. Molecular cancer research : MCR 86 24008674
1999 The LOXL2 gene encodes a new lysyl oxidase-like protein and is expressed at high levels in reproductive tissues. The Journal of biological chemistry 83 10212285
2019 Proteomic Profiling of Human Prostate Cancer-associated Fibroblasts (CAF) Reveals LOXL2-dependent Regulation of the Tumor Microenvironment. Molecular & cellular proteomics : MCP 81 31061140
2023 Mesenchymal stem cell-derived exosomal miR-27b-3p alleviates liver fibrosis via downregulating YAP/LOXL2 pathway. Journal of nanobiotechnology 80 37328872
2015 The function and mechanisms of action of LOXL2 in cancer (Review). International journal of molecular medicine 79 26329904
2012 LOXL2 in epithelial cell plasticity and tumor progression. Future oncology (London, England) 79 23030485
2020 Matrix stiffness-mediated effects on macrophages polarization and their LOXL2 expression. The FEBS journal 76 32964626
2014 Lysyl oxidase-like 2 (LOXL2) and E47 EMT factor: novel partners in E-cadherin repression and early metastasis colonization. Oncogene 76 24632622
2016 Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma. International journal of oncology 74 26983694
2014 Lysyl oxidase-like 2 (LOXL2) from stromal fibroblasts stimulates the progression of gastric cancer. Cancer letters 73 25128648
2022 Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma. Gut 71 35428659
2005 Switching on-off Snail: LOXL2 versus GSK3beta. Cell cycle (Georgetown, Tex.) 70 16294032
2013 LOXL2 expression is associated with invasiveness and negatively influences survival in breast cancer patients. Breast cancer research and treatment 68 23933800
2019 Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 61 30676771
2015 Tumour-suppressive microRNA-29s directly regulate LOXL2 expression and inhibit cancer cell migration and invasion in renal cell carcinoma. FEBS letters 61 26096783
2019 LOXL2 Upregulates Phosphorylation of Ezrin to Promote Cytoskeletal Reorganization and Tumor Cell Invasion. Cancer research 60 31409639
2019 LOXL2-A New Target in Antifibrogenic Therapy? International journal of molecular sciences 58 30986934
2016 Lysyl oxidase-like 2 (LOXL2) oxidizes trimethylated lysine 4 in histone H3. The FEBS journal 58 27735137
2015 Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma. International journal of oncology 58 26676674
2015 Tumor-suppressive microRNAs (miR-26a/b, miR-29a/b/c and miR-218) concertedly suppressed metastasis-promoting LOXL2 in head and neck squamous cell carcinoma. Journal of human genetics 55 26490187
2016 Regulation of LOXL2 and SERPINH1 by antitumor microRNA-29a in lung cancer with idiopathic pulmonary fibrosis. Journal of human genetics 53 27488440
2014 LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition. Biology open 51 24414204
2003 Reduction of LOX- and LOXL2-mRNA expression in head and neck squamous cell carcinomas. Anticancer research 50 12820424
2018 Upregulation of MIAT Regulates LOXL2 Expression by Competitively Binding MiR-29c in Clear Cell Renal Cell Carcinoma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 49 30041179
2021 The pathological significance of LOXL2 in pre-metastatic niche formation of HCC and its related molecular mechanism. European journal of cancer (Oxford, England : 1990) 47 33618200
2021 Novel mechanism for OSM-promoted extracellular matrix remodeling in breast cancer: LOXL2 upregulation and subsequent ECM alignment. Breast cancer research : BCR 45 34011405
2016 Emerging role of LOXL2 in the promotion of pancreas cancer metastasis. Oncotarget 45 27285767
2009 Functional analysis of LOXL2 in pancreatic carcinoma. International journal of colorectal disease 45 20012301
2022 HucMSCs-exosomes containing miR-21 promoted estrogen production in ovarian granulosa cells via LATS1-mediated phosphorylation of LOXL2 and YAP. General and comparative endocrinology 44 35271888
2011 The enzymatic activity of lysyl oxidas-like-2 (LOXL2) is not required for LOXL2-induced inhibition of keratinocyte differentiation. The Journal of biological chemistry 44 22157764
2010 Lysyl oxidase-like-2 (LOXL2) is a major isoform in chondrocytes and is critically required for differentiation. The Journal of biological chemistry 44 21071451
2016 SMYD3 stimulates EZR and LOXL2 transcription to enhance proliferation, migration, and invasion in esophageal squamous cell carcinoma. Human pathology 43 26980013
2013 The role of LOX and LOXL2 in scar formation after glaucoma surgery. Investigative ophthalmology & visual science 43 23821193
2023 LOXL4, but not LOXL2, is the critical determinant of pathological collagen cross-linking and fibrosis in the lung. Science advances 42 37235663
2015 LOXL2 Oxidizes Methylated TAF10 and Controls TFIID-Dependent Genes during Neural Progenitor Differentiation. Molecular cell 42 25959397
2008 TIMP-1 expression in human colorectal cancer is associated with TGF-B1, LOXL2, INHBA1, TNF-AIP6 and TIMP-2 transcript profiles. Molecular oncology 42 19383344
2018 LOXL2 promotes vasculogenic mimicry and tumour aggressiveness in hepatocellular carcinoma. Journal of cellular and molecular medicine 38 30506621
2017 MiR-504 inhibits cell proliferation and invasion by targeting LOXL2 in non small cell lung cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 38 29156517
2021 Reciprocal regulation of LOXL2 and HIF1α drives the Warburg effect to support pancreatic cancer aggressiveness. Cell death & disease 37 34836938
2014 LOXL2 status correlates with tumor stage and regulates integrin levels to promote tumor progression in ccRCC. Molecular cancer research : MCR 37 25092917
2014 Identification of a novel lysyl oxidase-like 2 alternative splicing isoform, LOXL2 Δe13, in esophageal squamous cell carcinoma. Biochemistry and cell biology = Biochimie et biologie cellulaire 36 25275797
2017 Role of LOXL2 in the epithelial-mesenchymal transition and colorectal cancer metastasis. Oncotarget 34 29113306
2019 Specific protein 1(SP1) regulates the epithelial-mesenchymal transition via lysyl oxidase-like 2(LOXL2) in pancreatic ductal adenocarcinoma. Scientific reports 33 30976063
2019 The interaction of LOXL2 with GATA6 induces VEGFA expression and angiogenesis in cholangiocarcinoma. International journal of oncology 33 31322171
2014 Lysyl oxidase-like 2 (LOXL2) controls tumor-associated cell proliferation through the interaction with MARCKSL1. Cellular signalling 33 24863880
2011 Down-regulation of lysyl oxidase-like 2 (LOXL2) is associated with disease progression in lung adenocarcinomas. Medical oncology (Northwood, London, England) 33 21519871
2018 LOXL2, a copper-dependent monoamine oxidase, activates lung fibroblasts through the TGF-β/Smad pathway. International journal of molecular medicine 32 30320382
2021 LOXL2-enriched small extracellular vesicles mediate hypoxia-induced premetastatic niche and indicates poor outcome of head and neck cancer. Theranostics 31 34646366
2019 LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells. Oncogene 31 31462706
2018 GINS2 promotes cell proliferation and inhibits cell apoptosis in thyroid cancer by regulating CITED2 and LOXL2. Cancer gene therapy 30 30177819
2019 miR-29a Is Repressed by MYC in Pancreatic Cancer and Its Restoration Drives Tumor-Suppressive Effects via Downregulation of LOXL2. Molecular cancer research : MCR 29 31662451
2013 LOXL2 induces aberrant acinar morphogenesis via ErbB2 signaling. Breast cancer research : BCR 29 23971878
2020 LOXL2 Expression Status Is Correlated With Molecular Characterizations of Cervical Carcinoma and Associated With Poor Cancer Survival via Epithelial-Mesenchymal Transition (EMT) Phenotype. Frontiers in oncology 27 32211324
2023 LOXL2 in Cancer: A Two-Decade Perspective. International journal of molecular sciences 26 37762708
2022 LOXL2-dependent deacetylation of aldolase A induces metabolic reprogramming and tumor progression. Redox biology 25 36209516
2020 LOXL2 upregulates hypoxia‑inducible factor‑1α signaling through Snail‑FBP1 axis in hepatocellular carcinoma cells. Oncology reports 25 32323822
2020 Linking LOXL2 to Cardiac Interstitial Fibrosis. International journal of molecular sciences 25 32824630
2018 Lysyl oxidase-like protein 2 (LOXL2) modulates barrier function in cholangiocytes in cholestasis. Journal of hepatology 24 29709678
2023 A protein complex of LCN2, LOXL2 and MMP9 facilitates tumour metastasis in oesophageal cancer. Molecular oncology 23 37753805
2019 Inhibition of LOXL2 Enhances the Radiosensitivity of Castration-Resistant Prostate Cancer Cells Associated with the Reversal of the EMT Process. BioMed research international 23 30809541
2024 RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling. Journal of experimental & clinical cancer research : CR 22 38326908
2019 Salidroside ameliorated hypoxia-induced tumorigenesis of BxPC-3 cells via downregulating hypoxia-inducible factor (HIF)-1α and LOXL2. Journal of cellular biochemistry 22 31162697
2017 Exome Sequencing Identifies LOXL2 Mutation as a Cause of Familial Intracranial Aneurysm. World neurosurgery 22 29107163
2015 The Role of LOX and LOXL2 in the Pathogenesis of an Experimental Model of Choroidal Neovascularization. Investigative ophthalmology & visual science 22 26258612
2023 Hypoxia preconditioned DPSC-derived exosomes regulate angiogenesis via transferring LOXL2. Experimental cell research 21 36894050
2022 GDNF Promotes Astrocyte Abnormal Proliferation and Migration Through the GFRα1/RET/MAPK/pCREB/LOXL2 Signaling Axis. Molecular neurobiology 21 35925441
2022 TRIM44 regulates tumor immunity in gastric cancer through LOXL2-dependent extracellular matrix remodeling. Cellular oncology (Dordrecht, Netherlands) 20 36512309
2023 Multiple Roles of LOXL2 in the Progression of Hepatocellular Carcinoma and Its Potential for Therapeutic Targeting. International journal of molecular sciences 19 37511503
2021 ZEB1 promotes colorectal cancer cell invasion and disease progression by enhanced LOXL2 transcription. International journal of clinical and experimental pathology 19 33532019
2021 MIR29A Impedes Metastatic Behaviors in Hepatocellular Carcinoma via Targeting LOX, LOXL2, and VEGFA. International journal of molecular sciences 19 34206143
2021 Deubiquitinase ZRANB1 drives hepatocellular carcinoma progression through SP1-LOXL2 axis. American journal of cancer research 19 34765294
2016 Escin Ia suppresses the metastasis of triple-negative breast cancer by inhibiting epithelial-mesenchymal transition via down-regulating LOXL2 expression. Oncotarget 19 27008697
2020 LOXL2 Upregulation in Gliomas Drives Tumorigenicity by Activating Autophagy to Promote TMZ Resistance and Trigger EMT. Frontiers in oncology 18 33194658
2016 The effect of LOXL2 in hepatocellular carcinoma. Molecular medicine reports 18 27430160
2016 Baicalein Inhibits Epithelial to Mesenchymal Transition via Downregulation of Cyr61 and LOXL-2 in MDA-MB231 Breast Cancer Cells. Molecules and cells 18 28008161
2021 LOXL2 attenuates osteoarthritis through inactivating Integrin/FAK signaling. Scientific reports 17 34426599
2020 LOXL2 promotes oncogenic progression in alveolar rhabdomyosarcoma independently of its catalytic activity. Cancer letters 17 31911079
2020 LOXL2 from human amniotic mesenchymal stem cells accelerates wound epithelialization by promoting differentiation and migration of keratinocytes. Aging 17 32621591
2020 Significance of nuclear LOXL2 inhibition in fibroblasts and myofibroblasts in the fibrotic process of acute respiratory distress syndrome. European journal of pharmacology 17 33248114
2023 Salidroside attenuates atrial fibrosis and atrial fibrillation vulnerability induced by angiotensin-II through inhibition of LOXL2-TGF-β1-Smad2/3 pathway. Heliyon 16 37920527
2022 LncRNA KCNQ1OT1-mediated cervical cancer progression by sponging miR-1270 as a ceRNA of LOXL2 through PI3k/Akt pathway. The journal of obstetrics and gynaecology research 16 35218109
2022 LOXL2 small molecule inhibitor restrains malignant transformation of cervical cancer cells by repressing LOXL2-induced epithelial-mesenchymal transition (EMT). Cell cycle (Georgetown, Tex.) 16 35509127
2020 LOXL2 promotes aggrecan and gender-specific anabolic differences to TMJ cartilage. Scientific reports 16 33214607
2023 Dihydroartemisinin Potentiates VEGFR-TKIs Antitumorigenic Effect on Osteosarcoma by Regulating Loxl2/VEGFA Expression and Lipid Metabolism Pathway. Journal of Cancer 15 37056396
2023 Irisin attenuates angiotensin II-induced atrial fibrillation and atrial fibrosis via LOXL2 and TGFβ1/Smad2/3 signaling pathways. Iranian journal of basic medical sciences 15 37275755

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