Affinage

LRIG1

Leucine-rich repeats and immunoglobulin-like domains protein 1 · UniProt Q96JA1

Round 2 corrected
Length
1093 aa
Mass
119.1 kDa
Annotated
2026-04-28
130 papers in source corpus 34 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LRIG1 is a transmembrane negative-feedback regulator of receptor tyrosine kinase signaling that constrains stem cell proliferation, maintains epithelial homeostasis, and functions as an inhibitory immune checkpoint receptor. Its extracellular leucine-rich repeat and immunoglobulin-like domains physically associate with multiple RTKs—including all four ErbB family members, Met, Ret, and TrkB—and LRIG1 promotes their ubiquitination and degradation by recruiting c-Cbl (for EGFR) or through Cbl-independent, USP8-regulated ubiquitination of LRIG1 itself (for Met), while its ADAM17-shed ectodomain suppresses EGFR signaling in a paracrine fashion (PMID:15282549, PMID:17178829, PMID:21087604, PMID:24828152). In vivo, LRIG1 loss causes epidermal hyperplasia, intestinal adenomas with elevated ErbB signaling, impaired neural stem cell quiescence, loss of interstitial cells of Cajal, and corneal degeneration driven by STAT3 hyperactivation (PMID:12067728, PMID:22464327, PMID:33972529, PMID:25921371, PMID:24316976). LRIG1 also serves as a receptor for the inhibitory ligand VISTA on CD8+ T cells, where it suppresses TCR signaling and enforces cytotoxic T lymphocyte quiescence; T cell-specific LRIG1 deletion enhances antitumor immunity (PMID:38758807).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 Medium

    Identification of LRIG1 (LIG-1) as a novel transmembrane glycoprotein with 15 LRRs and 3 Ig domains established its domain architecture and hinted at an adhesion/receptor function, but left its ligands and signaling role unknown.

    Evidence cDNA cloning, Northern blot, and in situ hybridization in mouse brain

    PMID:8798419

    Open questions at the time
    • No ligand or binding partner identified
    • Expression survey limited to brain
  2. 2001 Medium

    Mapping human LRIG1 to chromosome 3p14.3—a region of frequent cancer deletion—raised the possibility of tumor-suppressive function but provided no mechanistic insight.

    Evidence cDNA cloning and chromosomal mapping of human LRIG1

    PMID:11414704

    Open questions at the time
    • No functional data linking LRIG1 to tumor suppression
    • No protein-level characterization
  3. 2002 High

    Genetic ablation of Lrig1 in mice produced psoriasiform epidermal hyperplasia, demonstrating that LRIG1 is required to restrain keratinocyte proliferation in vivo and providing the first loss-of-function phenotype.

    Evidence Gene-targeted knockout mouse with histological analysis

    PMID:12067728

    Open questions at the time
    • Molecular target of LRIG1 in epidermis not identified
    • Signaling pathway not defined
  4. 2004 High

    Discovery that LRIG1 physically associates with all four ErbB receptors, recruits c-Cbl to promote EGFR ubiquitination and degradation, and is itself transcriptionally induced by EGF established the core negative-feedback mechanism by which LRIG1 attenuates RTK signaling.

    Evidence Reciprocal Co-IP, ubiquitylation assays, receptor half-life measurements, and transformation assays in multiple cell types

    PMID:15282549 PMID:15345710

    Open questions at the time
    • Whether c-Cbl recruitment is the universal mechanism for all RTK targets was untested
    • Structural basis of LRIG1–EGFR interaction unknown
  5. 2006 High

    Two advances broadened the LRIG1 model: the soluble LRR ectodomain was shown to bind EGFR with ~10 nM affinity and inhibit signaling extracellularly, while Lrig1 was identified as a Myc target marking junctional-zone epidermal stem cells capable of generating all epidermal lineages.

    Evidence Purified recombinant LRR domain binding/inhibition assays; single-cell profiling, skin reconstitution assays, and siRNA knockdown in keratinocytes

    PMID:16847455 PMID:16877544 PMID:19427292

    Open questions at the time
    • Paracrine ectodomain shedding mechanism not yet characterized
    • Whether LRIG1 marks stem cells in other epithelia was unknown
  6. 2006 High

    LRIG1 was shown to negatively regulate Met receptor stability independently of c-Cbl, revealing that LRIG1 uses distinct degradation mechanisms for different RTK targets.

    Evidence Co-IP, receptor half-life assays, siRNA knockdown, and invasion assays in breast cancer cells

    PMID:17178829

    Open questions at the time
    • Identity of the ubiquitin ligase or sorting machinery for Cbl-independent Met degradation was unknown
    • Whether Cbl-independence extends to other RTK targets untested
  7. 2008 High

    Extension of the pan-RTK inhibitor model: LRIG1 physically interacts with Ret, blocks GDNF binding and lipid-raft recruitment, and suppresses neurite outgrowth; separately, LRIG1 negatively regulates the oncogenic EGFRvIII mutant via a Cbl-independent trafficking mechanism.

    Evidence Co-IP, lipid raft fractionation, phosphorylation and neurite outgrowth assays (Ret); trafficking assays and siRNA in glioblastoma cells (EGFRvIII)

    PMID:18171921 PMID:18542056

    Open questions at the time
    • Structural determinants of LRIG1 selectivity across different RTKs not defined
    • In vivo validation of Ret regulation not provided
  8. 2010 Medium

    Demonstration that ADAM17 cleaves LRIG1 to release a soluble ectodomain that suppresses EGF signaling in neighboring cells in a paracrine fashion established a non-cell-autonomous mode of action.

    Evidence ADAM17 inhibitor (TAPI-2), ADAM17 overexpression, co-culture paracrine assays, tissue lysate immunoblotting

    PMID:21087604

    Open questions at the time
    • Cleavage site not mapped
    • In vivo relevance of paracrine signaling not established genetically
    • Mechanism of EGFR inhibition without receptor downregulation unclear
  9. 2012 High

    Lrig1 was established as a marker of quiescent intestinal stem cells and an in vivo tumor suppressor: Lrig1-null mice develop duodenal adenomas with elevated ErbB1-3, and Lrig1+ cells serve as the cell-of-origin for Apc-loss-driven adenomas, while separately LRIG3 was shown to functionally oppose LRIG1 by stabilizing ErbB receptors.

    Evidence Lineage tracing (Cre-lox), RNA-seq of Lrig1+ cells, Apc conditional deletion, intestinal organoid culture, receptor stability assays (LRIG3)

    PMID:22388892 PMID:22464327 PMID:23723069

    Open questions at the time
    • Whether LRIG1/LRIG3 opposition operates stoichiometrically or through distinct receptor pools unclear
    • Mechanistic basis of LRIG1-mediated stem cell quiescence beyond ErbB inhibition not defined
  10. 2013 High

    LRIG1 was linked to contact inhibition via a ternary complex with EGFR and E-cadherin, and independently shown to inhibit STAT3-dependent inflammation in the cornea; Lrig1-null corneas undergo a fate switch to keratinized epidermis rescued by STAT3 inhibition.

    Evidence Co-IP of ternary complex, Lrig1 KO airway and corneal phenotypes, STAT3 inhibitor rescue, bone marrow chimera experiments

    PMID:23208928 PMID:24316976

    Open questions at the time
    • Whether STAT3 regulation is direct or downstream of RTK inhibition not fully resolved
    • E-cadherin–LRIG1 interaction domain not mapped
  11. 2014 Medium

    Identification of USP8 as a LRIG1-specific deubiquitinase and elucidation of Cbl-independent Met degradation via LRIG1 ubiquitination and Hrs-mediated lysosomal sorting provided the missing machinery for the Cbl-independent degradation pathway.

    Evidence Co-IP, ubiquitination assays, lysosomal trafficking assays, USP8 siRNA knockdown

    PMID:23208509 PMID:24828152

    Open questions at the time
    • Whether USP8 regulates LRIG1 stability for all RTK targets not tested
    • E3 ligase responsible for LRIG1 ubiquitination in the Cbl-independent pathway not identified
  12. 2015 High

    Crystal structures of the LRIG1 LRR and 3Ig domains revealed a monomeric LRR and dimeric 3Ig architecture, but no direct binding to soluble EGFR was detected, indicating that transmembrane context or coreceptors are required for receptor engagement; concurrently, LRIG1 was validated as a direct transcriptional target of ERα and AR, integrating hormonal regulation into the LRIG1 feedback circuit.

    Evidence X-ray crystallography at 2.3 Å, biosensor binding assays (EGFR); ChIP for ERα and AR binding, domain mutants, xenograft models

    PMID:21821674 PMID:25765764 PMID:26148232 PMID:31792211

    Open questions at the time
    • Full-length LRIG1–EGFR complex structure not determined
    • Whether membrane anchoring or a coreceptor mediates the interaction is unknown
  13. 2015 High

    Lineage tracing demonstrated that Lrig1+ smooth muscle progenitors give rise to interstitial cells of Cajal (ICC), and Lrig1-null mice lose ICC markers and exhibit delayed intestinal transit, expanding LRIG1's physiological roles beyond epithelial homeostasis.

    Evidence Lrig1-CreERT2 lineage tracing, immunofluorescence for ICC markers, intestinal transit assays in knockout mice

    PMID:25921371

    Open questions at the time
    • RTK target responsible for ICC phenotype not identified
    • Whether LRIG1 acts cell-autonomously in ICC progenitors not confirmed
  14. 2016 High

    LRIG1 was shown to physically associate with TrkB and restrict BDNF-driven dendrite morphogenesis; Lrig1-null mice display altered proximal dendritic arborization and social interaction deficits, adding neurotrophic receptor regulation to the pan-RTK inhibitor model.

    Evidence Co-IP of TrkB–LRIG1, siRNA and Lrig1 KO in hippocampal neurons, behavioral analysis

    PMID:26935556

    Open questions at the time
    • Whether LRIG1 promotes TrkB degradation or only inhibits signaling not distinguished
    • Neural circuit basis of behavioral phenotype not mapped
  15. 2021 High

    LRIG1 was identified as a gatekeeper of neural stem cell exit from quiescence: BMP-4/FGF-2 primes quiescent NSCs by upregulating LRIG1, which allows EGFR accumulation while constraining its signaling, poising cells for re-entry; separately, LRIG1 and LRIG3 were shown to positively regulate BMP signaling and adipogenesis.

    Evidence Single-cell analysis, conditional Lrig1 KO in SVZ NSCs, BMP-4/FGF-2 quiescence assays; Lrig-null MEF adipogenesis rescue, C. elegans sma-10 genetics

    PMID:33469151 PMID:33972529

    Open questions at the time
    • Mechanism by which LRIG1 allows EGFR accumulation without signaling is not molecularly resolved
    • BMP receptor interaction with LRIG1 not demonstrated by direct binding
  16. 2022 Medium

    Epigenetic silencing of LRIG1 via promoter CpG methylation was demonstrated in triple-negative breast cancer; CRISPR/dCas9-TET1 targeted demethylation restored LRIG1 expression and reduced cancer cell viability, providing a mechanistic explanation for LRIG1 loss in tumors lacking genetic deletion.

    Evidence Methylation immunoprecipitation, 5-aza-2′-deoxycytidine treatment, CRISPR/dCas9-TET1 and dCas9-VP64 epigenetic editing

    PMID:35440669

    Open questions at the time
    • In vivo tumor suppression by demethylation not tested
    • Methylation status in other cancer types not systematically characterized in this study
  17. 2024 High

    A fundamentally new function was uncovered: LRIG1 is a receptor for the inhibitory ligand VISTA on CD8+ T cells; T cell-specific LRIG1 deletion expands tumor-specific cytotoxic T lymphocytes and enhances antitumor immunity, establishing LRIG1 as an immune checkpoint receptor beyond its RTK-regulatory roles.

    Evidence VISTA–LRIG1 binding assays, T cell-specific conditional knockout mice, tumor challenge models, CTL functional assays, flow cytometry

    PMID:38758807

    Open questions at the time
    • Structural basis of VISTA–LRIG1 interaction not determined
    • Whether LRIG1 immune checkpoint function is independent of its RTK regulation not fully resolved
    • Therapeutic potential of LRIG1 blockade not tested in combination immunotherapy

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length LRIG1–RTK complex structure explaining how transmembrane context enables receptor engagement (absent in isolated ectodomain), the identity of the E3 ligase for Cbl-independent RTK degradation, and the interplay between LRIG1's RTK-regulatory and immune checkpoint functions remain unresolved.
  • No full-length LRIG1–EGFR or LRIG1–VISTA co-structure
  • E3 ligase for Cbl-independent pathway unknown
  • Relative contribution of RTK inhibition vs. VISTA engagement to LRIG1 tumor suppression in vivo not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 8 GO:0060089 molecular transducer activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 1
Pathway
R-HSA-162582 Signal Transduction 11 R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 1
Partners
EGFRERBB2ERBB3ERBB4METNTRK2RETUSP8

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 LRIG1 (mouse LIG-1) was identified as a novel integral membrane glycoprotein containing 15 leucine-rich repeats, 3 immunoglobulin-like domains, a transmembrane region, and a cytoplasmic tail, with expression predominantly restricted to a subset of glial cells in the brain (Bergmann glia of cerebellum, olfactory bulb glia), suggesting a role as a cell-surface adhesion molecule or receptor. cDNA cloning, Northern blot, in situ hybridization, sequence analysis The Journal of biological chemistry Medium 8798419
2001 Human LIG1/LRIG1 was cloned and mapped to chromosome band 3p14.3 (a region frequently deleted in cancer); predicted to encode a transmembrane cell-surface protein homologous to Drosophila Kekkon-1, with highest expression in brain and lowest in spleen. cDNA cloning, chromosomal mapping, RT-PCR expression analysis Biochemical and biophysical research communications Medium 11414704
2002 Targeted disruption of LIG-1/LRIG1 in mice causes psoriasiform epidermal hyperplasia, demonstrating that LRIG1 is required to restrain epidermal keratinocyte proliferation in vivo; LRIG1 is expressed in basal epidermal cells and outer root sheath cells. Gene targeting (knockout mouse), histology, in situ hybridization FEBS letters High 12067728
2003 LRIG1 protein migrates as two species (~143 kDa and ~134 kDa) under reducing conditions and can be cleaved into an N-terminal ~111 kDa fragment and a C-terminal ~32 kDa fragment; cell-surface biotinylation and confocal microscopy confirmed LRIG1 localizes to the plasma membrane. Immunoblotting, cell-surface biotinylation, confocal microscopy with LRIG1-GFP fusion protein Cell and tissue research Medium 12684867
2004 LRIG1 transcript and protein are upregulated upon EGF stimulation; LRIG1 physically associates with all four ErbB/EGFR family members (EGFR/ErbB1, ErbB2, ErbB3, ErbB4); LRIG1 upregulation leads to enhanced ubiquitylation and degradation of EGFR by recruiting the E3 ubiquitin ligase c-Cbl, which simultaneously ubiquitylates both EGFR and LRIG1 and sorts them to degradation, establishing LRIG1 as a feedback negative attenuator of ErbB signaling. Co-immunoprecipitation, ubiquitylation assays, immunoblotting, EGF stimulation experiments The EMBO journal High 15282549
2004 LRIG1 forms a complex with each ErbB receptor (EGFR, ErbB2, ErbB3, ErbB4) independent of growth factor binding in co-transfected cells; LRIG1 co-expression suppresses cellular EGFR levels, shortens receptor half-life, and enhances ligand-stimulated receptor ubiquitination, suppressing EGF-stimulated transformation of NIH3T3 fibroblasts and cell cycle progression in PC3 prostate tumor cells. Co-immunoprecipitation in 293T cells, receptor half-life assays, ubiquitination assays, soft agar transformation assay, cell cycle analysis The Journal of biological chemistry High 15345710
2006 A soluble ectodomain of LRIG1 containing only the leucine-rich repeat (LRR) domain inhibits ligand-independent and ligand-dependent EGFR activation and causes growth inhibition of EGFR-expressing carcinoma cells; high-affinity binding sites (Kd ~10 nM) for the LRIG1 ectodomain exist on EGFR-expressing cells, competitively displaced by EGF, indicating the LRR domain engages EGFR extracellularly. Cell growth inhibition assays, competitive binding assays, phosphorylation assays, ERK1/2 signaling assays with purified recombinant protein Oncogene High 16847455
2006 Lrig1 is a Myc target gene in mouse epidermis; loss of Lrig1 increases the proliferative capacity of epidermal stem cells in culture and causes epidermal hyperproliferation in vivo; Lrig1-expressing cells at the hair follicle junctional zone can give rise to all adult epidermal lineages (sebaceous gland, interfollicular epidermis) in skin reconstitution assays; siRNA knockdown in human keratinocytes increases cell-surface EGFR levels, enhances downstream pathway activation, and stimulates proliferation; Lrig1 also negatively regulates the Myc promoter. Single-cell expression profiling, siRNA knockdown, Lrig1 overexpression, flow cytometry, immunofluorescence, skin reconstitution assay, clonal growth analysis Proceedings of the National Academy of Sciences of the United States of America / Cell stem cell High 16877544 19427292
2006 LRIG1 is a novel negative regulator of the Met receptor tyrosine kinase; LRIG1 interacts with Met independent of HGF stimulation and destabilizes Met in a Cbl-independent manner; LRIG1 overexpression reduces endogenous Met in breast cancer cells, impairs HGF responses, and opposes Met/ErbB2 synergy in driving cellular invasion; RNAi knockdown of LRIG1 increases Met receptor half-life. Co-immunoprecipitation, receptor half-life assays, siRNA knockdown, invasion assays, overexpression in breast cancer cells Molecular and cellular biology High 17178829
2008 Lrig1 physically interacts with the Ret receptor tyrosine kinase and inhibits GDNF binding to Ret, prevents Ret recruitment to lipid rafts, blocks receptor autophosphorylation, and suppresses MAPK activation in response to GDNF; Lrig1 overexpression inhibits GDNF/Ret-induced neurite outgrowth cell-autonomously; Lrig1 siRNA knockdown potentiates neuronal differentiation and MAPK activation in response to GDNF. Co-immunoprecipitation, lipid raft fractionation, phosphorylation assays, siRNA knockdown, neurite outgrowth assays The Journal of neuroscience High 18171921
2008 LRIG1 negatively regulates the oncogenic EGFRvIII mutant; EGFRvIII retains interaction with LRIG1 and is more sensitive to LRIG1 action than wild-type EGFR; LRIG1 regulation of EGFRvIII is distinct from Cbl-mediated degradation and alters EGFRvIII intracellular trafficking; LRIG1 RNAi silencing leads to enhanced EGFRvIII expression. Co-immunoprecipitation, siRNA knockdown, receptor trafficking assays, proliferation/survival/motility/invasion assays in glioblastoma cells Oncogene High 18542056
2008 LRIG1 protein levels are suppressed by ErbB receptor activation in breast tumor cells (but not in non-transformed breast epithelial cells), creating a feed-forward regulatory loop where aberrant ErbB2 signaling suppresses LRIG1, which in turn contributes to ErbB2 overexpression; RNAi-mediated LRIG1 knockdown further elevates ErbB2 and augments proliferation. siRNA knockdown, ectopic expression, immunoblotting, ErbB activation experiments in breast cancer cell lines and transgenic mouse tumors Cancer research Medium 18922900
2010 LRIG1 ectodomains are constitutively shed from the cell surface by metalloprotease activity (enhanced by ADAM17/TAPI-2-sensitive mechanism); shed LRIG1 ectodomains function in a paracrine manner to suppress EGF signaling in co-cultured cells without apparent downregulation of EGFR levels; shedding occurs in vivo as demonstrated by immunoblotting of tissue lysates. ADAM17 inhibitor treatment (TAPI-2), ADAM17 ectopic expression, co-culture assays, immunoblotting of conditioned media and tissue lysates Experimental cell research Medium 21087604
2012 Lrig1 marks predominantly noncycling, long-lived intestinal stem cells at the crypt base; transcriptome profiling shows Lrig1+ colonic stem cells upregulate cell cycle repression and oxidative damage response genes; genetic ablation of Lrig1 results in heightened ErbB1-3 expression and duodenal adenomas; loss of Apc in Lrig1+ cells leads to intestinal adenomas, establishing Lrig1 as a pan-ErbB inhibitor, intestinal stem cell marker, and tumor suppressor in vivo. Lineage mapping (Cre-lox), transcriptome profiling (RNA-seq), genetic ablation (knockout mice), Apc conditional deletion Cell High 22464327
2012 Lrig1 controls the size of the intestinal stem cell niche by regulating the amplitude of ErbB growth factor signaling; Lrig1 is a negative-feedback regulator highly expressed in intestinal stem cells, and its loss expands the stem cell compartment; ErbB activation is established as a strong inductive signal for intestinal stem cell proliferation. Genetic loss-of-function (knockout mice), intestinal organoid culture, ErbB signaling assays Nature cell biology High 22388892
2012 LRIG1 and LRIG3 functionally oppose one another: Lrig3 stabilizes ErbB receptors and opposes Lrig1 negative regulatory activity, while Lrig1 destabilizes Lrig3, identifying Lrig3 as a new target of Lrig1; this cross-talk regulates ErbB receptor levels. Co-immunoprecipitation, receptor stability assays, gain/loss-of-function overexpression experiments The Journal of biological chemistry Medium 23723069
2013 LRIG1 forms a ternary complex with EGFR and E-cadherin to regulate contact inhibition; loss of Lrig1 is sufficient to promote murine airway hyperplasia through loss of contact inhibition; re-expression of LRIG1 in human lung cancer cells inhibits tumourigenesis; LRIG1 modulates EGFR activity downstream of E-cadherin-mediated cell-cell contact. Co-immunoprecipitation (ternary complex), Lrig1 knockout mouse (airway hyperplasia phenotype), re-expression in lung cancer cell lines, proliferation and tumourigenesis assays The Journal of pathology Medium 23208928
2013 LRIG1 inhibits STAT3-dependent inflammatory signaling to maintain corneal homeostasis; Lrig1 deletion in mice results in impaired stem cell recruitment after injury and a cell-fate switch to keratinized skin-like epidermis leading to corneal blindness; inhibition of STAT3 in Lrig1-/- mice rescues pathological phenotypes; bone marrow chimera experiments show LRIG1 also coordinates bone marrow-derived inflammatory cell function. Knockout mouse (Lrig1-/-), STAT3 inhibition rescue experiments, transgenic STAT3 activation, bone marrow chimera experiments, wound repair assays The Journal of clinical investigation High 24316976
2013 LRIG1 modulates aggressiveness of head and neck cancers via the EGFR-MAPK-SPHK1 signaling pathway; inducible LRIG1 expression suppresses EGFR ligands/activators, MMPs, and SPHK1; LRIG1 also triggers integrin inactivation and reduces SNAI2, coupling EGFR signaling suppression to extracellular matrix remodeling. Inducible expression system, gene expression profiling, ChIP, western blotting, in vitro and in vivo tumor growth assays Oncogene Medium 23624915
2014 USP8 is a LRIG1-specific deubiquitinating enzyme that interacts with LRIG1 and stabilizes it; the anti-Met antibody SAIT301 induces ubiquitination of LRIG1, promoting recruitment of Met/LRIG1 complex to the lysosome via Hrs interaction, leading to concomitant degradation of both LRIG1 and Met; USP8 inhibition reduces LRIG1 stability and impairs Met degradation. Co-immunoprecipitation, ubiquitination assays, lysosomal trafficking assays, siRNA knockdown of USP8 Scientific reports Medium 24828152
2014 Anti-Met antibody SAIT301 mediates Cbl-independent Met degradation via LRIG1; LRIG1 enables Met downregulation without receptor activation, providing a mechanistic basis for non-agonistic Met-targeting therapy; LRIG1-mediated Met degradation is effective even in tumors with low/no Cbl expression or Met exon 14 deletion. Co-immunoprecipitation, receptor degradation assays, tumor xenograft models, Cbl-deficient cell lines Oncogene Medium 23208509
2015 LRIG1 is downregulated during epithelial-to-mesenchymal transition (EMT) of human mammary epithelial cells; LRIG1 depletion expands the stem cell population and accelerates EMT; LRIG1 expression in basal-B breast cancer cells provokes mesenchymal-to-epithelial transition, suppresses tumorsphere formation and invasive growth, and perturbs multiple RTK signaling pathways. siRNA knockdown, ectopic expression, 3D invasion assays, tumorsphere formation, EMT marker analysis, in vivo xenograft growth Oncogene Medium 26387542
2015 LRIG1 regulates the postnatal development of interstitial cells of Cajal (ICC-DMP and ICC-SMP) from LRIG1-positive smooth muscle progenitors; Lrig1-null mice lose KIT, anoctamin-1, and neurokinin 1 receptor staining in DMP and SMP regions and exhibit significant delays in small intestinal transit. Lineage tracing (Lrig1-CreERT2 × Rosa26-LSL-YFP), immunofluorescence, intestinal transit assays in Lrig1-null mice Gastroenterology High 25921371
2015 The LRIG1 extracellular domain crystal structures were determined for the LRR domain and 3Ig domain at 2.3 Å resolution; the LRR domain and LRR-1Ig fragment are monomeric in solution while the 3Ig domain is dimeric; notably, no direct binding of isolated LRIG1 domains to soluble or cell-surface EGFR was detected by biosensor analysis, suggesting the full-length transmembrane context is required for receptor interaction. X-ray crystallography (2.3 Å), biosensor binding assays, baculovirus expression, analytical ultracentrifugation Journal of molecular biology High 25765764
2015 LRIG1 is an estrogen receptor α (ERα) target gene; estrogen stimulates LRIG1 accumulation, and disruption of estrogen induction enhances estrogen-dependent tumor cell growth; ErbB2 activation antagonizes ERα-driven LRIG1 expression; an LRIG1 mutant lacking the ErbB3 interaction motif cannot downregulate ErbB3, and LRIG1 loss in fulvestrant-treated cells permits ErbB3 upregulation and enhanced survival signaling. ChIP, ectopic expression, LRIG1 domain mutants, immunoblotting, ERα activation/inhibition experiments, cell growth assays Oncogene / Molecular cancer research High 21821674 26148232
2016 Lrig1 physically interacts with TrkB and attenuates BDNF signaling; Lrig1 knockdown in hippocampal neurons enhances primary dendrite formation and proximal dendritic branching; Lrig1-deficient mice display morphological changes in proximal dendrite arborization and defects in social interaction; Lrig1 restricts BDNF-induced dendrite morphology in a cell-intrinsic manner. Co-immunoprecipitation (TrkB-Lrig1), siRNA knockdown, gain/loss-of-function in hippocampal neurons, Lrig1-/- mouse behavioral and morphological analysis EMBO reports High 26935556
2018 A yeast two-hybrid screen and BioPlex data mining identified a LRIG1 protein interaction network including RAB4A, PON2, GAL3ST1, ZBTB16, LRIG2, CNPY3, HLA-DRA, GML, CNPY4, LRRC40, LRIG3, GLRX3, and PTPRK as functionally relevant LRIG1 interactors; PON2 co-localizes with LRIG1 and functionally promotes LRIG1-mediated PDGFRα downregulation. Yeast two-hybrid screen, shRNA functional evaluation in triple co-transfection system, BioPlex data mining, co-localization imaging The Journal of biological chemistry Medium 29317492
2019 Androgen receptor (AR) directly transactivates LRIG1 through binding to AR-binding sites in the LRIG1 locus; LRIG1 dampens ERBB expression in a cell-type-dependent manner; LRIG1 exhibits tumor-suppressive functions in both AR+ and AR- prostate cancer xenograft models and inhibits ERBB2-driven tumor growth; transgenic LRIG1 inhibits tumor development in Hi-Myc and TRAMP mouse models. ChIP (AR binding to LRIG1 locus), xenograft models, transgenic mouse models (Hi-Myc, TRAMP), siRNA/ectopic expression, ERBB signaling analysis Nature communications High 31792211
2021 LRIG1 is a gatekeeper of neural stem cell (NSC) exit from quiescence; BMP-4 signaling induces a dormant quiescent NSC state while combined BMP-4/FGF-2 signaling induces a primed quiescent state with high LRIG1 and CD9; genetic disruption of Lrig1 in SVZ NSCs leads to enhanced proliferation; mechanistically, LRIG1 enables EGFR protein levels to increase while limiting EGFR signaling activation, priming cells for cell cycle re-entry. Single-cell analysis, in vitro quiescence induction (BMP-4/FGF-2), Lrig1 conditional knockout in SVZ, EGFR signaling assays, engraftment into adult SVZ Nature communications High 33972529
2021 LRIG proteins (LRIG1 and LRIG3 but not LRIG2) regulate BMP signaling; Lrig-null mouse embryonic fibroblasts are deficient in adipogenesis and BMP signaling, and this defect is rescued by LRIG1 or LRIG3 ectopic expression; C. elegans sma-10/LRIG mutants exhibit a lipid storage defect, demonstrating evolutionary conservation of LRIG function in BMP/lipid metabolism. Lrig-null MEF adipogenesis assays, BMP signaling assays, ectopic expression rescue, C. elegans genetic analysis Communications biology Medium 33469151
2022 Aberrant promoter CpG island methylation of LRIG1 is most prominent in basal/triple-negative breast cancer; global demethylation with 5-aza-2'-deoxycytidine restores LRIG1 expression; CRISPR/dCas9-mediated targeted TET1 demethylation and VP64 transcriptional activation at the LRIG1 CpG island increases LRIG1 expression and reduces cancer cell viability, demonstrating epigenetic silencing as a mechanism of LRIG1 repression. Methylation immunoprecipitation, 5-aza-2'-deoxycytidine treatment, CRISPR/dCas9-TET1 and dCas9-VP64 targeted demethylation/activation, qRT-PCR, immunoblotting British journal of cancer Medium 35440669
2024 LRIG1 is a VISTA (V-domain immunoglobulin suppressor of T cell activation) binding partner that acts as an inhibitory immune checkpoint receptor on CD8+ T cells; T cell-specific LRIG1 deletion in mice leads to expansion of tumor-specific cytotoxic T lymphocytes with increased effector function, superior antitumor responses, and reduced quiescent CTL populations; LRIG1 suppresses T cell receptor signaling pathways upon VISTA engagement. VISTA-LRIG1 binding assays, T cell-specific conditional knockout mice, tumor challenge models, CTL functional assays, flow cytometry of T cell subsets Science immunology High 38758807

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2012 The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell 576 22464327
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2009 Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis. Cell stem cell 426 19427292
2012 Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling. Nature cell biology 340 22388892
2010 Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction. Nature genetics 289 21076409
2006 Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence. Proceedings of the National Academy of Sciences of the United States of America 253 16877544
2012 Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations. Nature genetics 241 22797727
2004 LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation. The EMBO journal 236 15282549
2004 The leucine-rich repeat protein LRIG1 is a negative regulator of ErbB family receptor tyrosine kinases. The Journal of biological chemistry 193 15345710
2011 Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque. Nature genetics 170 21909108
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2001 Cloning, characterization, and expression of human LIG1. Biochemical and biophysical research communications 119 11414704
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2006 LRIG1 is a novel negative regulator of the Met receptor and opposes Met and Her2 synergy. Molecular and cellular biology 107 17178829
2002 Targeted disruption of LIG-1 gene results in psoriasiform epidermal hyperplasia. FEBS letters 96 12067728
2008 Lrig1 is an endogenous inhibitor of Ret receptor tyrosine kinase activation, downstream signaling, and biological responses to GDNF. The Journal of neuroscience : the official journal of the Society for Neuroscience 94 18171921
2008 Suppression of the negative regulator LRIG1 contributes to ErbB2 overexpression in breast cancer. Cancer research 93 18922900
2021 NLRP7 deubiquitination by USP10 promotes tumor progression and tumor-associated macrophage polarization in colorectal cancer. Journal of experimental & clinical cancer research : CR 90 33838681
2013 The interfollicular epidermis of adult mouse tail comprises two distinct cell lineages that are differentially regulated by Wnt, Edaradd, and Lrig1. Stem cell reports 89 24052938
2021 SARS-CoV-2-host proteome interactions for antiviral drug discovery. Molecular systems biology 86 34709727
2002 Is LRIG1 a tumour suppressor gene at chromosome 3p14.3? Acta oncologica (Stockholm, Sweden) 77 12234026
1996 cDNA cloning of a novel membrane glycoprotein that is expressed specifically in glial cells in the mouse brain. LIG-1, a protein with leucine-rich repeats and immunoglobulin-like domains. The Journal of biological chemistry 72 8798419
2013 LRIG1 is a triple threat: ERBB negative regulator, intestinal stem cell marker and tumour suppressor. British journal of cancer 71 23558895
2021 LRIG1 is a gatekeeper to exit from quiescence in adult neural stem cells. Nature communications 70 33972529
2007 LRIG1 and squamous epithelial uterine cervical cancer: correlation to prognosis, other tumor markers, sex steroid hormones, and smoking. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 67 17624990
2003 LRIG1 and epidermal growth factor receptor in renal cell carcinoma: a quantitative RT--PCR and immunohistochemical analysis. British journal of cancer 65 14520461
2008 LRIG1 negatively regulates the oncogenic EGF receptor mutant EGFRvIII. Oncogene 64 18542056
2012 Cbl-independent degradation of Met: ways to avoid agonism of bivalent Met-targeting antibody. Oncogene 63 23208509
2006 A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity. Oncogene 59 16847455
2011 Lrig1 is an estrogen-regulated growth suppressor and correlates with longer relapse-free survival in ERα-positive breast cancer. Molecular cancer research : MCR 58 21821674
2003 LRIG1 protein in human cells and tissues. Cell and tissue research 58 12684867
2013 LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis. The Journal of clinical investigation 56 24316976
2017 Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomach. Gut 52 28814482
2013 The soluble form of the tumor suppressor Lrig1 potently inhibits in vivo glioma growth irrespective of EGF receptor status. Neuro-oncology 52 23723255
2014 Inducible loss of one Apc allele in Lrig1-expressing progenitor cells results in multiple distal colonic tumors with features of familial adenomatous polyposis. American journal of physiology. Gastrointestinal and liver physiology 51 24833705
2013 LRIG1 modulates aggressiveness of head and neck cancers by regulating EGFR-MAPK-SPHK1 signaling and extracellular matrix remodeling. Oncogene 51 23624915
2019 Structure of the UHRF1 Tandem Tudor Domain Bound to a Methylated Non-histone Protein, LIG1, Reveals Rules for Binding and Regulation. Structure (London, England : 1993) 48 30639225
2019 LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling. Science (New York, N.Y.) 47 31073040
2016 Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling. EMBO reports 46 26935556
2023 hsa_circ_0007919 induces LIG1 transcription by binding to FOXA1/TET1 to enhance the DNA damage response and promote gemcitabine resistance in pancreatic ductal adenocarcinoma. Molecular cancer 44 38044421
2014 Expression of LRIG1 is associated with good prognosis and human papillomavirus status in oropharyngeal cancer. British journal of cancer 44 24548859
2011 Arabidopsis ARP endonuclease functions in a branched base excision DNA repair pathway completed by LIG1. The Plant journal : for cell and molecular biology 44 21781197
2009 Upregulation of LRIG1 suppresses malignant glioma cell growth by attenuating EGFR activity. Journal of neuro-oncology 42 19300910
2024 LRIG1 engages ligand VISTA and impairs tumor-specific CD8+ T cell responses. Science immunology 41 38758807
2018 Isoliquiritigenin suppresses human melanoma growth by targeting miR-301b/LRIG1 signaling. Journal of experimental & clinical cancer research : CR 41 30081934
2013 Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects. PloS one 41 24324551
2010 Paracrine regulation of growth factor signaling by shed leucine-rich repeats and immunoglobulin-like domains 1. Experimental cell research 41 21087604
2013 Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. Cancer science 40 23648065
2011 LRIG1 and the liar paradox in prostate cancer: a study of the expression and clinical significance of LRIG1 in prostate cancer. International journal of cancer 39 21128282
2018 The oncogenic RNA-binding protein SRSF1 regulates LIG1 in non-small cell lung cancer. Laboratory investigation; a journal of technical methods and pathology 36 30181552
2015 LRIG1 inhibits hypoxia-induced vasculogenic mimicry formation via suppression of the EGFR/PI3K/AKT pathway and epithelial-to-mesenchymal transition in human glioma SHG-44 cells. Cell stress & chaperones 35 25860915
2012 Downregulation of LRIG1 expression by RNA interference promotes the aggressive properties of glioma cells via EGFR/Akt/c-Myc activation. Oncology reports 35 23124613
2012 Expression of LRIG1 and LRIG3 correlates with human papillomavirus status and patient survival in cervical adenocarcinoma. International journal of oncology 35 23165628
2021 C5orf51 is a component of the MON1-CCZ1 complex and controls RAB7A localization and stability during mitophagy. Autophagy 33 34432599
2015 LRIG1 opposes epithelial-to-mesenchymal transition and inhibits invasion of basal-like breast cancer cells. Oncogene 33 26387542
2013 LRIG1 regulates cadherin-dependent contact inhibition directing epithelial homeostasis and pre-invasive squamous cell carcinoma development. The Journal of pathology 33 23208928
2013 VCP phosphorylation-dependent interaction partners prevent apoptosis in Helicobacter pylori-infected gastric epithelial cells. PloS one 33 23383273
2018 Lrig1 is a haploinsufficient tumor suppressor gene in malignant glioma. Oncogenesis 32 29391393
2018 Downregulation of leucine-rich repeats and immunoglobulin-like domains 1 by microRNA-20a modulates gastric cancer multidrug resistance. Cancer science 32 29450946
2013 Gambogic acid induces EGFR degradation and Akt/mTORC1 inhibition through AMPK dependent-LRIG1 upregulation in cultured U87 glioma cells. Biochemical and biophysical research communications 32 23665322
2013 Leucine-rich repeat and immunoglobulin domain-containing protein-1 (Lrig1) negative regulatory action toward ErbB receptor tyrosine kinases is opposed by leucine-rich repeat and immunoglobulin domain-containing protein 3 (Lrig3). The Journal of biological chemistry 32 23723069
2021 Potential Novel Genes for Late-Onset Alzheimer's Disease in East-Asian Descent Identified by APOE-Stratified Genome-Wide Association Study. Journal of Alzheimer's disease : JAD 31 34151794
2013 LRIG1 dictates the chemo-sensitivity of temozolomide (TMZ) in U251 glioblastoma cells via down-regulation of EGFR/topoisomerase-2/Bcl-2. Biochemical and biophysical research communications 30 23850692
2012 LRIG1 modulates cancer cell sensitivity to Smac mimetics by regulating TNFα expression and receptor tyrosine kinase signaling. Cancer research 30 22241084
2018 Downregulation of microRNA-4295 enhances cisplatin-induced gastric cancer cell apoptosis through the EGFR/PI3K/Akt signaling pathway by targeting LRIG1. International journal of oncology 29 30320337
2020 LncRNA MAGI2-AS3 inhibits the self-renewal of leukaemic stem cells by promoting TET2-dependent DNA demethylation of the LRIG1 promoter in acute myeloid leukaemia. RNA biology 28 32174258
2019 LRIG1 is a pleiotropic androgen receptor-regulated feedback tumor suppressor in prostate cancer. Nature communications 28 31792211
2018 A protein interaction network centered on leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) regulates growth factor receptors. The Journal of biological chemistry 28 29317492
2017 Overexpressed miR-183 promoted glioblastoma radioresistance via down-regulating LRIG1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 29793318
2015 LRIG1 is a prognostic biomarker in non-small cell lung cancer. Acta oncologica (Stockholm, Sweden) 28 25813475
2014 Loss of LRIG1 locus increases risk of early and late relapse of stage I/II breast cancer. Cancer research 28 24879564
2007 LRIG1 expression in colorectal cancer. Acta oncologica (Stockholm, Sweden) 28 17851870
2022 Mechanism of human Lig1 regulation by PCNA in Okazaki fragment sealing. Nature communications 27 36539424
2019 Targeted mobilization of Lrig1+ gastric epithelial stem cell populations by a carcinogenic Helicobacter pylori type IV secretion system. Proceedings of the National Academy of Sciences of the United States of America 27 31488717
2014 USP8 modulates ubiquitination of LRIG1 for Met degradation. Scientific reports 27 24828152
2021 LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes. Communications biology 26 33469151
2021 LRIG1, a regulator of stem cell quiescence and a pleiotropic feedback tumor suppressor. Seminars in cancer biology 26 33476721
2023 TRIM67 drives tumorigenesis in oligodendrogliomas through Rho GTPase-dependent membrane blebbing. Neuro-oncology 25 36215168
2021 microRNA-1246-containing extracellular vesicles from acute myeloid leukemia cells promote the survival of leukemia stem cells via the LRIG1-meditated STAT3 pathway. Aging 25 33893245
2015 LRIG1 Regulates Ontogeny of Smooth Muscle-Derived Subsets of Interstitial Cells of Cajal in Mice. Gastroenterology 25 25921371
2015 miR-20a mediates temozolomide-resistance in glioblastoma cells via negatively regulating LRIG1 expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 25 25960225
2017 HPV8 Field Cancerization in a Transgenic Mouse Model Is due to Lrig1+ Keratinocyte Stem Cell Expansion. The Journal of investigative dermatology 24 28595997
2006 LRIG1, a candidate tumour-suppressor gene in human bladder cancer cell line BIU87. BJU international 24 16978290
2019 LRIG1 acts as a critical regulator of melanoma cell invasion, migration, and vasculogenic mimicry upon hypoxia by regulating EGFR/ERK-triggered epithelial-mesenchymal transition. Bioscience reports 23 30487162
2013 A role for LRIG1 in the regulation of malignant glioma aggressiveness. International journal of oncology 23 23337938
2015 Loss of Lrig1 leads to expansion of Brunner glands followed by duodenal adenomas with gastric metaplasia. The American journal of pathology 22 25794708
2007 Redistribution of LRIG proteins in psoriasis. The Journal of investigative dermatology 22 18037903
2015 LRIG1, human EGFR inhibitor, reverses multidrug resistance through modulation of ABCB1 and ABCG2. Brain research 21 25801120
2022 Structures of LIG1 that engage with mutagenic mismatches inserted by polβ in base excision repair. Nature communications 20 35790757
2020 Lrig1 expression prospectively identifies stem cells in the ventricular-subventricular zone that are neurogenic throughout adult life. Neural development 20 32183906
2018 Tumor-suppressive effect of LRIG1, a negative regulator of ErbB, in non-small cell lung cancer harboring mutant EGFR. Carcinogenesis 20 29546323
2017 Harnessing LRIG1-mediated inhibition of receptor tyrosine kinases for cancer therapy. Biochimica et biophysica acta. Reviews on cancer 20 28259645
2016 Association between Single-Nucleotide Polymorphisms of the hOGG1,NEIL1,APEX1, FEN1,LIG1, and LIG3 Genes and Alzheimer's Disease Risk. Neuropsychobiology 20 27010693
2022 Aberrant promoter methylation contributes to LRIG1 silencing in basal/triple-negative breast cancer. British journal of cancer 19 35440669
2021 LIG1 syndrome mutations remodel a cooperative network of ligand binding interactions to compromise ligation efficiency. Nucleic acids research 19 33444456
2015 LRIG1 enhances the radiosensitivity of radioresistant human glioblastoma U251 cells via attenuation of the EGFR/Akt signaling pathway. International journal of clinical and experimental pathology 19 26097540
2012 Lrig1: a new master regulator of epithelial stem cells. The EMBO journal 19 22433838
2015 LRIG1, a 3p tumor suppressor, represses EGFR signaling and is a novel epigenetic silenced gene in colorectal cancer. Biochemical and biophysical research communications 18 26159916
2013 Restoration of LRIG1 suppresses bladder cancer cell growth by directly targeting EGFR activity. Journal of experimental & clinical cancer research : CR 18 24314030
2020 LRIG1-Mediated Inhibition of EGF Receptor Signaling Regulates Neural Precursor Cell Proliferation in the Neocortex. Cell reports 17 33053360
2014 Using a new Lrig1 reporter mouse to assess differences between two Lrig1 antibodies in the intestine. Stem cell research 17 25460603
2017 MicroRNA-590-3p enhances the radioresistance in glioblastoma cells by targeting LRIG1. Experimental and therapeutic medicine 16 28810655
2017 From the Cover: High Susceptibility of Lrig1 Sebaceous Stem Cells to TCDD in Mice. Toxicological sciences : an official journal of the Society of Toxicology 15 28973660
2020 Evaluation of the influence of chronic low-dose radiation on DNA repair gene polymorphisms [XRCC1, XRCC3, PRKDC (XRCC7), LIG1, NEIL1] in individuals from normal and high level natural radiation areas of Kerala Coast. International journal of radiation biology 14 32149571
2015 Decreased LRIG1 in fulvestrant-treated luminal breast cancer cells permits ErbB3 upregulation and increased growth. Oncogene 14 26148232
1999 Phytochrome-induced expression of lig1, a homologue of the fission yeast cell-cycle checkpoint gene hus1, is associated with the developmental switch in Physarum polycephalum plasmodia. Current genetics 14 10447599
2021 LRIG1 is a conserved EGFR regulator involved in melanoma development, survival and treatment resistance. Oncogene 13 33947959
2018 Expression of LRIG1, a Negative Regulator of EGFR, Is Dynamically Altered during Different Stages of Gastric Carcinogenesis. The American journal of pathology 13 30248341
2024 Structures of LIG1 provide a mechanistic basis for understanding a lack of sugar discrimination against a ribonucleotide at the 3'-end of nick DNA. The Journal of biological chemistry 12 38522520
2015 Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin. Oncology reports 12 25695283
2015 LRIG1 extracellular domain: structure and function analysis. Journal of molecular biology 12 25765764
2014 LRIG1 as a potential novel marker for neoplastic transformation in ocular surface squamous neoplasia. PloS one 12 24709893
2024 Unfilled gaps by polβ lead to aberrant ligation by LIG1 at the downstream steps of base excision repair pathway. Nucleic acids research 11 38366780
2018 Resveratrol inhibits glioma cell growth via targeting LRIG1. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 11 29745084
2017 Senescent Atrophic Epidermis Retains Lrig1+ Stem Cells and Loses Wnt Signaling, a Phenotype Shared with CD44KO Mice. PloS one 11 28099467
2011 Suppression of bladder cancer cell tumorigenicity in an athymic mouse model by adenoviral vector-mediated transfer of LRIG1. Oncology reports 11 21567105
2024 Dysregulation and antimetastatic function of circLRIG1 modulated by miR-214-3p/LRIG1 axis in bladder carcinoma. Biology direct 10 38454507
2022 Lrig1 regulates the balance between proliferation and quiescence in glioblastoma stem cells. Frontiers in cell and developmental biology 10 36420140
2020 MicroRNA Expression Profiling of Normal and Malignant Human Colonic Stem Cells Identifies miRNA92a as a Regulator of the LRIG1 Stem Cell Gene. International journal of molecular sciences 10 32316543
2012 LRIG1 enhances cisplatin sensitivity of glioma cell lines. Oncology research 10 23581227
2011 LRIG1 combined with cisplatin enhances bladder cancer lesions via a novel pathway. Oncology reports 10 21431282
2015 Association Between the LIG1 Polymorphisms and Lung Cancer Risk: A Meta-analysis of Case-Control Studies. Cell biochemistry and biophysics 9 27352326
2014 Single-nucleotide polymorphisms of LIG1 associated with risk of lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 9 24929328
2007 Down-regulation of leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) in HP75 pituitary adenoma cell line. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 9 17393120