Affinage

COL11A1

Collagen alpha-1(XI) chain · UniProt P12107

Length
1806 aa
Mass
181.1 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COL11A1 encodes the α1 chain of type XI collagen, a minor fibrillar collagen that nucleates heterotypic collagen fibrils and regulates their diameter in cartilage and other connective tissues; it is essential for skeletal morphogenesis, craniofacial development, and auditory function. Loss-of-function in mice causes chondrodysplasia with disordered growth plate architecture and abnormally thick collagen fibrils, while in humans, heterozygous dominant-negative mutations cause Stickler syndrome type 2 and Marshall syndrome, biallelic null mutations cause lethal fibrochondrogenesis, and splice-site mutations cause nonsyndromic hearing loss (DFNA37) (PMID:7859283, PMID:8872475, PMID:9529347, PMID:21035103, PMID:30245514). The N-terminal non-collagenous domain is surface-exposed on fibrils and interacts with proteoglycans and matricellular proteins to regulate fibrillogenesis, while basal transcription in chondrocytes requires NF-Y binding to the proximal promoter and Sp1 binding to a GC-rich element (PMID:22038862, PMID:12805369, PMID:26487428). In cancer, COL11A1 is expressed by cancer-associated fibroblasts and tumor cells, where it stabilizes PDK1 to activate Akt signaling, drives NF-κB-dependent transcription of pro-survival genes, promotes epithelial-mesenchymal transition via AKT/GSK-3β/Snail, and establishes a positive-feedback loop with IL-6/ATF4 to sustain chemoresistance and stromal activation (PMID:26087191, PMID:34117361, PMID:35327583, PMID:36861686).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 High

    Establishing that COL11A1 is essential for cartilage fibril organization and skeletal morphogenesis resolved the question of whether type XI collagen is structurally required or merely accessory in cartilage ECM.

    Evidence Molecular identification of the cho/cho frameshift mutation in Col11a1 in mice with chondrodysplasia, wide limb bones, and disrupted growth plates

    PMID:7859283

    Open questions at the time
    • Mechanism by which α1(XI) controls fibril diameter not defined at the molecular level
    • Role in non-cartilaginous tissues expressing Col11a1 not tested
  2. 1995 Medium

    Demonstrating tissue-specific alternative splicing of the N-terminal variable region (exons 6A/6B) and broad embryonic expression beyond cartilage indicated that COL11A1 contributes to ECM organization in multiple organ systems.

    Evidence Exon-specific in situ hybridization and immunohistochemistry in mouse embryos showing differential exon 6A/6B distribution across skeletal, smooth muscle, and neural tissues

    PMID:8530046 PMID:8563024

    Open questions at the time
    • Functional consequence of each splice isoform not directly tested
    • Whether different trimeric partners form in non-cartilage tissues is unknown
  3. 1996 High

    Identifying a glycine substitution in COL11A1 as the cause of Stickler syndrome type 2 established this gene as a human disease gene and showed that the triple-helical domain is critical for vitreous collagen integrity.

    Evidence Linkage analysis and mutation identification (Gly97Val) cosegregating with vitreous/retinal disease in a family

    PMID:8872475

    Open questions at the time
    • Structural basis for dominant-negative disruption not resolved
    • Whether all glycine substitutions are equally pathogenic is unclear
  4. 1999 High

    Systematic genotype-phenotype analysis distinguished Marshall syndrome (in-frame exon-skipping mutations in the C-terminal triple helix) from Stickler syndrome, revealing regional functional domains within the COL11A1 triple helix.

    Evidence Screening 23 novel mutations across COL11A1 in Marshall and Stickler families with splice-site characterization by RT-PCR

    PMID:10486316 PMID:9529347

    Open questions at the time
    • Structural basis for region-specific phenotypic differences not determined
    • Whether interallelic complementation modulates severity is unknown
  5. 2003 High

    Identifying NF-Y as a direct transcriptional activator of the COL11A1 proximal promoter provided the first defined mechanism for basal COL11A1 transcription in chondrocytes.

    Evidence ChIP, EMSA, reporter assays, and dominant-negative NF-YA experiments in chondrocyte cell lines

    PMID:12805369 PMID:24092017

    Open questions at the time
    • Chondrocyte-specific cofactors beyond NF-Y and Sp1 not identified
    • Chromatin-level regulation (enhancers, epigenetic marks) largely unexplored
  6. 2003 Medium

    Showing that Col11a1 haploinsufficiency does not cause hearing loss while dominant-negative mutations do established that Stickler/Marshall hearing phenotypes result from poisoning of wild-type collagen fibrils, not simple dosage reduction.

    Evidence ABR threshold measurement in cho/+ versus wild-type mice across multiple ages

    PMID:12527136

    Open questions at the time
    • Molecular mechanism of dominant-negative interference in the cochlear tectorial membrane not defined
    • Whether cochlear fibril diameter changes parallel the cartilage phenotype is untested
  7. 2009 High

    Zebrafish col11a1 knockdown confirmed an evolutionarily conserved role in fibril diameter regulation and additionally revealed a requirement for chondrocyte hypertrophic maturation, linking ECM composition to chondrocyte differentiation.

    Evidence Morpholino knockdown in zebrafish with electron microscopy of fibrils, in situ hybridization, and histological analysis

    PMID:19638309

    Open questions at the time
    • Whether the chondrocyte maturation defect is cell-autonomous or secondary to matrix disorganization is unclear
    • Signaling pathway connecting fibril defects to differentiation not identified
  8. 2010 High

    Identification of biallelic null COL11A1 mutations causing lethal fibrochondrogenesis — and later, demonstration that alternative splicing of exon 9 modulates severity — established a dose-dependent allelic series from null (lethal) through dominant-negative (Stickler/Marshall) phenotypes.

    Evidence SNP genotyping and autozygosity mapping in fibrochondrogenesis cases; minigene splicing assays and allele-specific RT-PCR for exon 9 effects

    PMID:21035103 PMID:23922384

    Open questions at the time
    • Residual function of partially spliced alleles not quantified at the protein level
    • Whether modifier genes influence phenotypic severity is unknown
  9. 2011 Medium

    Affinity chromatography with the N-terminal non-collagenous domain identified proteoglycans and matricellular proteins as direct binding partners, establishing this domain as a molecular hub on the fibril surface for ECM interactions.

    Evidence Recombinant N-terminal domain affinity pulldown from fetal bovine cartilage with LC-MS/MS identification

    PMID:22038862

    Open questions at the time
    • Individual interactions not validated by reciprocal binding or functional assays
    • Binding affinities and stoichiometries not determined
  10. 2015 High

    Discovery that COL11A1 binds PDK1 and attenuates its ubiquitination, stabilizing Akt signaling to promote chemoresistance, revealed a non-structural oncogenic function for COL11A1 as a signaling ligand in cancer.

    Evidence Co-IP of COL11A1-PDK1, ubiquitination assays, shRNA knockdown, and overexpression in ovarian cancer cells with cisplatin/paclitaxel resistance readouts

    PMID:26087191

    Open questions at the time
    • Receptor mediating COL11A1-PDK1 interaction not identified
    • Whether PDK1 stabilization is direct or through an intermediate adaptor is unclear
  11. 2016 Medium

    Elucidation of COL11A1-driven NF-κB activation via SP1 phosphorylation and IKKβ upregulation, leading to TWIST1/Mcl-1 transcription, expanded the downstream signaling repertoire linking COL11A1 to survival and invasion programs.

    Evidence siRNA knockdown in ovarian cancer cells with western blotting for phospho-SP1, IKKβ, TWIST1, and chemosensitivity assays

    PMID:28815582

    Open questions at the time
    • How COL11A1 activates ERK/SP1 phosphorylation at the receptor level is undefined
    • Relative contribution of NF-κB versus Akt pathways to chemoresistance not dissected
  12. 2021 High

    Demonstration that COL11A1 activates CAFs through NF-κB/IGFBP2/TGF-β3 and establishes a positive-feedback IL-6/ATF4 loop with tumor cells unified the paracrine and autocrine circuits by which COL11A1 remodels the tumor microenvironment.

    Evidence Co-culture, ChIP for p65 on IGFBP2 promoter, xenograft rescue with anti-TGF-β3 antibody; parallel study showing IL-6/MAPK/ATF4 feedback driving COL11A1 transcription in PDAC-CAF co-cultures

    PMID:34117361 PMID:36861686

    Open questions at the time
    • Cell-surface receptor on CAFs that senses COL11A1 is not identified
    • Whether the feedback loop operates in non-ovarian/non-pancreatic cancers is untested
  13. 2021 High

    Finding that somatic COL11A1 mutations in cutaneous SCC induce β1-integrin-dependent invasion — and non-cell-autonomously promote neighboring wild-type cell invasion — revealed a gain-of-function oncogenic mechanism distinct from the secreted wild-type protein's role.

    Evidence CRISPR knockin of mutant COL11A1 in keratinocytes, xenograft tumorigenesis, mosaic tissue invasion assays

    PMID:34584216

    Open questions at the time
    • Which specific mutations are gain-of-function versus loss-of-function is not systematically classified
    • Structural basis for mutant COL11A1 activating β1 integrin is unknown
  14. 2024 Medium

    Identification of a PAX1-COL11A1-MMP3 axis in spinal chondrocytes and the demonstration that COL11A1 loss shifts chondrocyte metabolism from glycolysis to OXPHOS via HIF1α, driving cellular senescence, expanded COL11A1's role to a metabolic regulator of chondrocyte homeostasis.

    Evidence CRISPR Pax1-KO mice, Col11a1-KO mice, scRNA-seq, Col11a1-overexpressing SMSC organoid rescue in DDH model

    PMID:38277211 PMID:38314968

    Open questions at the time
    • Direct molecular link between COL11A1 and HIF1α stabilization is undefined
    • Whether the metabolic shift is a direct intracellular effect or secondary to ECM changes is unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The cell-surface receptor(s) through which extracellular COL11A1 activates Akt, NF-κB, and integrin signaling in cancer cells and fibroblasts remain unidentified, leaving the proximal step of its oncogenic signaling undefined.
  • No receptor identification study performed
  • Whether COL11A1 signals as intact trimer, processed fragment, or monomeric chain is unknown
  • Structural basis for COL11A1-PDK1 interaction not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 3
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 4 R-HSA-1474244 Extracellular matrix organization 3
Partners
ATF4COL2A1IGFBP2NF-YPAX1PDK1SP1
Complex memberships
Type XI collagen heterotrimer (α1(XI)/α2(XI)/α1(II))

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 COL11A1 (Col11a1) is essential for normal cartilage collagen fibril formation and cohesive properties of cartilage; homozygous loss-of-function mutation (frameshift/premature stop) in cho/cho mice causes chondrodysplasia with abnormally wide, short limb bones and disrupted growth plate chondrocyte organization. Mouse genetic model (cho/cho autosomal recessive mutation), linkage analysis, mRNA sequencing, histology Cell High 7859283
1995 Alternative splicing of Col11a1 exons 6A and 6B produces isoforms with distinct acidic or basic N-terminal peptides; the two isoforms show tissue-specific distribution in mouse embryo (exon 6B predominant in vertebrae and skeletal muscle; exon 6A in smooth muscle of intestine, aorta, lung), suggesting distinct contributions to tissue-specific matrix assembly. In situ hybridization with exon-specific cDNA probes, immunohistochemistry with peptide-specific antibodies in mouse embryo tissues Genomics / Matrix biology Medium 11246003 8530046
1995 Col11a1 transcripts are expressed developmentally from embryonic day 11 in mouse, predominantly in cartilaginous tissues (chondrocranium, developing limbs) but also in neuro-epithelium, odontoblasts, trabecular bone, atrioventricular valve, tongue, intestine, and otic vesicle, indicating broader expression than previously thought and suggesting the α1(XI) chain may form tissue-specific trimers. In situ hybridization on mouse embryo sections Developmental dynamics Medium 8563024
1996 A Gly97Val substitution in the triple helical domain of COL11A1 causes Stickler syndrome type 2 with vitreous and retinal abnormalities, establishing COL11A1 as a structural component of human vitreous and demonstrating that dominant-negative glycine substitutions in the triple helix disrupt vitreous collagen architecture. Linkage analysis, single-base mutation identification (G→T), genotype-phenotype correlation in affected family Human molecular genetics High 8872475
1998 A splice-donor-site mutation (G+1→A) in COL11A1 causes in-frame skipping of a 54-bp exon, deleting amino acids 726–743 from the major triple-helical domain, and segregates with Marshall syndrome, demonstrating that α1(XI) collagen structural integrity in the triple-helical domain is required for normal skeletal morphogenesis. Mutation identification and cosegregation analysis, RT-PCR/splicing characterization of mutant transcript American journal of human genetics High 9529347
1999 Splicing mutations that cause in-frame skipping of specific 54-bp exons in the C-terminal region of COL11A1 produce a dominant-negative truncated α1(XI) chain and are specifically associated with the Marshall syndrome phenotype, whereas null-allele mutations in COL2A1 produce classic Stickler syndrome; this genotype-phenotype correlation reveals that the C-terminal triple-helical region of COL11A1 is critical for craniofacial/skeletal morphogenesis. Genomic structure characterization of COL11A1, mutation screening of 23 novel mutations, genotype-phenotype correlation American journal of human genetics High 10486316
2001 COL11A1 expression in colorectal tumors is associated with an active APC/β-catenin (Wnt) signaling pathway; COL11A1 upregulation co-occurs with WISP-1 (a Wnt target), suggesting Wnt pathway activation drives stromal COL11A1 expression. RT-PCR differential display, FAP patient tissue analysis, correlation with Wnt pathway markers in 37 sporadic colorectal carcinomas BMC cancer Low 11707154
2001 In Col11a1 mutant (cho/cho) mice, cleft palate arises primarily because mandibular growth disruption prevents palatal shelf contact, not from intrinsic failure of medial-edge epithelium (MEE) to undergo epithelial-mesenchymal transformation; cho/cho palatal shelves retain full EMT capacity when brought into contact in vitro. In vitro palatal shelf culture, carboxydichlorofluorescein succinimidyl ester fate-tracing of MEE Archives of oral biology Medium 11420059
2003 The transcription factor CBF/NF-Y directly binds an ATTGG sequence in the proximal COL11A1 promoter (−147 to −121 region) and is required for basal transcriptional activation; dominant-negative NF-Y significantly inhibits promoter activity. EMSA, chromatin immunoprecipitation, interference/supershift assays, transient and stable transfection reporter assays, DNA-affinity-purified protein binding The Journal of biological chemistry High 12805369
2004 Col11a1 mRNA is expressed in the greater epithelial ridge as the main source for the tectorial membrane in the developing mouse cochlea, with later focal expression in inner sulcus and Claudius'/Boettcher's cells; this localization defines the cochlear cell populations responsible for type XI collagen in the tectorial/basilar membranes and underlies hearing function. In situ hybridization on mouse temporal bones at multiple developmental time points Acta oto-laryngologica Medium 15141750
2003 Col11a1 haploinsufficiency (cho/+ heterozygotes) does not cause significant hearing loss in mice; therefore, Stickler/Marshall syndrome COL11A1 mutations cause hearing loss via dominant-negative effects on wild-type fibrillar collagen polypeptides in the cochlear extracellular matrix, not through simple haploinsufficiency. Auditory brainstem response (ABR) threshold measurement in cho/+ versus +/+ mice at multiple ages Hearing research Medium 12527136
2009 In zebrafish, col11a1 knockdown disrupts craniofacial cartilage formation and notochord morphology; chondrocyte spatial organization, cartilage element shaping, and chondrocyte hypertrophic maturation are all impaired; knockdown also increases col2a1 expression and results in abnormally thick, sparse fibrils in cartilage ECM, demonstrating that col11a1 regulates fibril diameter and chondrocyte differentiation. Morpholino-based knockdown in zebrafish, in situ hybridization, real-time PCR, histology/electron microscopy of cartilage ECM Matrix biology High 19638309
2010 Biallelic loss-of-function COL11A1 mutations (compound heterozygosity for null allele + glycine substitution) cause fibrochondrogenesis, a severe lethal skeletal dysplasia, establishing that complete loss of α1(XI) collagen function is more severe than heterozygous dominant-negative mutations causing Stickler/Marshall syndrome. Whole-genome SNP genotyping, autozygosity mapping, mutation sequencing in two independent fibrochondrogenesis cases American journal of human genetics High 21035103
2011 The amino-terminal non-collagenous domain of collagen α1(XI), displayed on the surface of heterotypic cartilage collagen fibrils, interacts with proteoglycans, other collagens, and matricellular molecules; affinity chromatography with this domain from fetal bovine cartilage identified multiple ECM binding partners by LC-MS/MS, supporting a role for the N-terminal domain in fibrillogenesis regulation. Affinity chromatography with recombinant N-terminal domain, liquid chromatography/tandem mass spectrometry (LC-MS/MS) protein identification Proteomics Medium 22038862
2013 Alternative splicing of exon 9 of COL11A1 modifies the phenotypic severity of biallelic mutations; alleles that retain exon 9 splicing can produce a normal α1(XI) procollagen molecule, converting the phenotype from fibrochondrogenesis to recessive Stickler syndrome type 2 with profound hearing loss. Mutation sequencing, minigene splicing reporter assays, allele-specific RT-PCR, clinical phenotyping Journal of medical genetics High 23922384
2013 NF-Y (nuclear factor Y) directly binds an ATTGG sequence in the proximal Col11a1 promoter in chondrocytes and is required for its activity; dominant-negative NF-YA inhibits promoter activity, and ChIP confirms in vivo binding. Transient transfection reporter assays, EMSA, chromatin immunoprecipitation, siRNA/dominant-negative overexpression in chondrocytes In vitro cellular & developmental biology High 24092017
2014 COL11A1/procollagen 11A1 is expressed by TGF-β1-activated immortalized human bone marrow mesenchymal cells and by cancer-associated fibroblasts (CAFs) of human colon adenocarcinoma, but not by normal fibroblasts or normal colon stromal cells; proCOL11A1+ CAFs co-express vimentin and αSMA (myofibroblast markers). qRT-PCR, immunocytochemistry with validated anti-proCOL11A1 monoclonal antibody, immunohistochemistry of colon adenocarcinomas and normal tissues BMC cancer Medium 25417197
2015 COL11A1 promotes chemoresistance in ovarian cancer cells through activation of the Akt/C/EBPβ signaling pathway; COL11A1 binds to PDK1, attenuates PDK1 ubiquitination and degradation, and thereby stabilizes PDK1 to promote cell survival; C/EBPβ binding to the COL11A1 promoter drives cisplatin/paclitaxel-induced COL11A1 upregulation. Co-immunoprecipitation, immunofluorescence, shRNA knockdown, COL11A1 overexpression, ubiquitination assay, promoter binding assay, microarray analysis Oncotarget High 26087191
2015 Col11a1 depletion in mice results in altered trabecular bone microstructure and increased bone collar thickness during endochondral ossification, demonstrating a role for Col11a1 in regulating bone microarchitecture and mineralization during embryonic development. X-ray microtomography (micro-CT), histology of Col11a1-deficient versus wild-type mice Journal of developmental biology Medium 26779434
2015 Sp1 transcription factor upregulates Col11a1 proximal promoter activity by binding a GC-rich element (−96 to −67) in chondrocytes; Sp1 siRNA knockdown suppresses endogenous Col11a1 transcript levels. Luciferase reporter assays with deletion/mutation constructs, in silico analysis, Sp1 overexpression and siRNA knockdown in chondrocytes In vitro cellular & developmental biology Medium 26487428
2016 COL11A1 promotes ovarian cancer chemoresistance by activating NF-κB signaling via increased SP1 phosphorylation and ERK activation, leading to IKKβ upregulation and TWIST1/Mcl-1/GAS6 expression; COL11A1 siRNA knockdown increases chemosensitivity to cisplatin and paclitaxel via downregulated TWIST1. siRNA knockdown, western blotting, reporter assays, SP1 phosphorylation analysis, gene expression profiling in ovarian cancer cell lines International journal of cancer Medium 28815582
2016 COL11A1 overexpression promotes NSCLC cell proliferation, migration, invasion, and cisplatin resistance in vitro; these effects are mediated through Smad signaling; COL11A1 suppression by shRNA causes G1-phase cell cycle arrest and reduced cyclin D1, and elevated p21/cleaved caspase-3. shRNA knockdown, cell proliferation/migration/invasion assays, western blotting, cDNA microarray analysis with RT-PCR validation Oncology reports Medium 27373316
2018 A canonical acceptor splice-site variant (c.652-2A>C) in COL11A1 confirmed in vitro to alter RNA splicing causes autosomal dominant nonsyndromic hearing loss (DFNA37), expanding the COL11A1 phenotypic spectrum beyond syndromic collagenopathies. Genome-wide linkage analysis (LOD 8.29), exome sequencing, in vitro splicing assay, genotyping of 48 family members Genetics in medicine High 30245514
2021 COL11A1 activates cancer-associated fibroblasts by triggering ERK-mediated SP1 phosphorylation, which promotes p65 nuclear translocation and NF-κB-driven IGFBP2 expression, ultimately activating TGF-β3; this CAF-cancer cell crosstalk induces IL-6 secretion promoting EOC cell proliferation and invasiveness; in vivo, COL11A1 overexpression promotes tumor formation and CAF activation reversible by anti-TGF-β3 antibody. Co-culture experiments, conditioned medium assays, shRNA/overexpression in human ovarian fibroblasts, western blotting, ChIP for p65 binding to IGFBP2 promoter, mouse xenograft model, TGF-β3 antibody rescue Oncogene High 34117361
2021 COL11A1 activates the Akt/CREB pathway in pancreatic cancer cells, phosphorylating AktSer473 and shifting the BCL-2/BAX balance toward anti-apoptosis; COL11A1/Akt disrupts mitochondrial transmembrane potential, inhibits cytochrome c release and Apaf-1/procaspase-9/Cyt-C complex formation, suppressing the intrinsic apoptosis program and promoting gemcitabine resistance. COL11A1 overexpression/siRNA knockdown in PDAC cell lines, western blotting for Akt/CREB/BCL-2/BAX/caspase-9/cytochrome c, mitochondrial translocation assays Journal of Cancer Medium 33531986
2021 Mutant COL11A1 (identified in 66/100 cutaneous SCCs, concentrated in the triple-helical domain) promotes tumorigenesis and accelerates neoplastic invasion by inducing β1 integrin targets; knockout of mutant COL11A1 impairs cSCC tumorigenesis in vivo; mosaic mutant COL11A1 cells also enhance invasion by neighboring wild-type cells in trans. Tumor sequencing, gene editing (CRISPR-generated mutant COL11A1 knockin), in vivo xenograft tumorigenesis, gene expression analysis (β1 integrin pathway), mosaic tissue invasion assays Oncogene High 34584216
2022 COL11A1 promotes epithelial-mesenchymal transition (EMT) and stemness in pancreatic cancer cells by activating the AKT/GSK-3β/Snail signaling axis, increasing p-AKTSer473, p-GSK-3βSer9, and Snail, thereby facilitating invasion and migration. siRNA/plasmid overexpression, Transwell invasion/migration assays, western blotting, flow cytometry, clone formation Biomolecules Medium 35327583
2021 miR-335 directly inhibits COL11A1 transcription in ovarian cancer cells; miR-335-mediated COL11A1 suppression reduces invasiveness via the Ets-1/MMP3 axis and reduces chemoresistance via the Akt/C/EBPβ/PDK1 axis, including increased PDK1 ubiquitination and degradation. miRNA mimic/inhibitor transfection, reporter assays, Akt/PDK1/ubiquitination western blots, in vivo miR-335 expression in EOC samples Cancers Medium 34944877
2024 Wild-type COL11A1 expression in costal chondrocytes suppresses PAX1 and MMP3 expression; the AIS-associated COL11A1P1335L mutant abrogates suppression of MMP3, implicating a PAX1-COL11A1-MMP3 signaling axis in spinal chondrocytes; estrogen receptor (ESR2) knockdown or tamoxifen treatment also alters Col11a1 and Mmp3 expression in chondrocytes. GWAS and exome sequencing (genetic mapping), CRISPR Pax1-knockout mice, scRNA-seq, protein co-localization in spinal tissue, genetic targeting (Col11a1 overexpression in chondrocytes), ESR2 siRNA knockdown, tamoxifen treatment eLife High 38277211
2024 Col11a1-KO mice show aggravated joint degeneration and OA phenotype with disrupted chondrocyte homeostasis; scRNA-seq reveals that COL11A1 loss causes a shift from glycolysis to OXPHOS metabolism mediated by HIF1α, leading to chondrocyte cellular senescence; Col11a1-overexpressing SMSC organoids ameliorate cartilage degeneration in DDH mice by restoring HIF1α-mediated glycolysis. Col11a1-KO mice, scRNA-seq of DDH and KO cartilage, Col11a1 overexpression in SMSC organoids, intra-articular injection, histology Clinical and translational medicine Medium 38314968
2024 COL11A1 overexpression confers tamoxifen resistance in breast cancer cells by elevating estrogen receptor α (ERα) expression and its downstream target genes; COL11A1 knockdown decreases ERα and sensitizes tamoxifen-resistant cells to 4-OHT in vitro and in vivo. Stable COL11A1 overexpression in MCF-7/T47D, tamoxifen-resistant cell line generation, siRNA knockdown, xenograft model, western blotting for ERα pathway NPJ breast cancer Medium 38806505
2021 PDAC-derived COL11A1 promotes conversion of normal fibroblasts to CAF-like cells via NF-κB pathway activation; CAFs then secrete IL-6, which promotes PDAC cell invasion and EMT, and IL-6 activates the MAPK/ERK pathway to increase ATF4, which directly transcribes COL11A1, forming a positive feedback loop between PDAC cells and CAFs. Co-culture experiments, siRNA knockdown, western blotting for NF-κB/ERK/ATF4/COL11A1, PDAC-CAF interaction assays Cell biology international Medium 36861686

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 A fibrillar collagen gene, Col11a1, is essential for skeletal morphogenesis. Cell 301 7859283
1996 A family with Stickler syndrome type 2 has a mutation in the COL11A1 gene resulting in the substitution of glycine 97 by valine in alpha 1 (XI) collagen. Human molecular genetics 221 8872475
1999 Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes. American journal of human genetics 183 10486316
2001 Colorectal carcinogenesis is associated with stromal expression of COL11A1 and COL5A2. Carcinogenesis 145 11375892
2010 Multi-cancer computational analysis reveals invasion-associated variant of desmoplastic reaction involving INHBA, THBS2 and COL11A1. BMC medical genomics 129 21047417
2007 A functional polymorphism in COL11A1, which encodes the alpha 1 chain of type XI collagen, is associated with susceptibility to lumbar disc herniation. American journal of human genetics 128 17999364
2018 Meta-analysis of Icelandic and UK data sets identifies missense variants in SMO, IL11, COL11A1 and 13 more new loci associated with osteoarthritis. Nature genetics 124 30374069
2010 Stickler syndrome and the vitreous phenotype: mutations in COL2A1 and COL11A1. Human mutation 107 20513134
2015 COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human invasive carcinoma-associated stromal cells and carcinoma progression. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 101 25761876
1998 Marshall syndrome associated with a splicing defect at the COL11A1 locus. American journal of human genetics 97 9529347
2016 A COL11A1-correlated pan-cancer gene signature of activated fibroblasts for the prioritization of therapeutic targets. Cancer letters 96 27609069
2021 Collagen Type XI Alpha 1 (COL11A1): A Novel Biomarker and a Key Player in Cancer. Cancers 89 33668097
2006 Great potential of a panel of multiple hMTH1, SPD, ITGA11 and COL11A1 markers for diagnosis of patients with non-small cell lung cancer. Oncology reports 89 17016581
2015 COL11A1 confers chemoresistance on ovarian cancer cells through the activation of Akt/c/EBPβ pathway and PDK1 stabilization. Oncotarget 86 26087191
2016 COL11A1 is overexpressed in recurrent non-small cell lung cancer and promotes cell proliferation, migration, invasion and drug resistance. Oncology reports 78 27373316
2021 COL11A1 activates cancer-associated fibroblasts by modulating TGF-β3 through the NF-κB/IGFBP2 axis in ovarian cancer cells. Oncogene 69 34117361
2013 Overexpression of COL11A1 by cancer-associated fibroblasts: clinical relevance of a stromal marker in pancreatic cancer. PloS one 66 24194920
2007 A report on 10 new patients with heterozygous mutations in the COL11A1 gene and a review of genotype-phenotype correlations in type XI collagenopathies. American journal of medical genetics. Part A 64 17236192
1999 Stickler syndrome: further mutations in COL11A1 and evidence for additional locus heterogeneity. European journal of human genetics : EJHG 63 10573014
1995 Developmental pattern of expression of the mouse alpha 1 (XI) collagen gene (Col11a1). Developmental dynamics : an official publication of the American Association of Anatomists 62 8563024
2010 Fibrochondrogenesis results from mutations in the COL11A1 type XI collagen gene. American journal of human genetics 60 21035103
2017 Activation of TWIST1 by COL11A1 promotes chemoresistance and inhibits apoptosis in ovarian cancer cells by modulating NF-κB-mediated IKKβ expression. International journal of cancer 58 28815582
2021 Single-cell analysis reveals the pan-cancer invasiveness-associated transition of adipose-derived stromal cells into COL11A1-expressing cancer-associated fibroblasts. PLoS computational biology 51 34283835
2001 COL11A1 in FAP polyps and in sporadic colorectal tumors. BMC cancer 48 11707154
2014 Novel pathogenic COL11A1/COL11A2 variants in Stickler syndrome detected by targeted NGS and exome sequencing. Molecular genetics and metabolism 46 25240749
2023 Single-cell analysis reveals the COL11A1+ fibroblasts are cancer-specific fibroblasts that promote tumor progression. Frontiers in pharmacology 44 36744260
2016 COL11A1 is overexpressed in gastric cancer tissues and regulates proliferation, migration and invasion of HGC-27 gastric cancer cells in vitro. Oncology reports 44 28004111
2018 Splice-altering variant in COL11A1 as a cause of nonsyndromic hearing loss DFNA37. Genetics in medicine : official journal of the American College of Medical Genetics 42 30245514
2019 Akt inhibitor SC66 promotes cell sensitivity to cisplatin in chemoresistant ovarian cancer cells through inhibition of COL11A1 expression. Cell death & disease 41 30975980
2022 SPP1 facilitates cell migration and invasion by targeting COL11A1 in lung adenocarcinoma. Cancer cell international 40 36266702
2021 The COL11A1/Akt/CREB signaling axis enables mitochondrial-mediated apoptotic evasion to promote chemoresistance in pancreatic cancer cells through modulating BAX/BCL-2 function. Journal of Cancer 40 33531986
2013 Alternative splicing modifies the effect of mutations in COL11A1 and results in recessive type 2 Stickler syndrome with profound hearing loss. Journal of medical genetics 40 23922384
2011 Splicing analysis of unclassified variants in COL2A1 and COL11A1 identifies deep intronic pathogenic mutations. European journal of human genetics : EJHG 35 22189268
2009 Craniofacial cartilage morphogenesis requires zebrafish col11a1 activity. Matrix biology : journal of the International Society for Matrix Biology 34 19638309
2001 The mechanism of palatal clefting in the Col11a1 mutant mouse. Archives of oral biology 33 11420059
2021 Circ-0005105 activates COL11A1 by targeting miR-20a-3p to promote pancreatic ductal adenocarcinoma progression. Cell death & disease 32 34183642
2014 Validation of COL11A1/procollagen 11A1 expression in TGF-β1-activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma. BMC cancer 32 25417197
2022 COL11A1 as an novel biomarker for breast cancer with machine learning and immunohistochemistry validation. Frontiers in immunology 31 36389832
2015 Col11a1 Regulates Bone Microarchitecture during Embryonic Development. Journal of developmental biology 31 26779434
2023 Collagen 1A1 (COL1A1) and Collagen11A1(COL11A1) as diagnostic biomarkers in Breast, colorectal and gastric cancers. Gene 30 37783295
2014 Extended association study of PLEKHA7 and COL11A1 with primary angle closure glaucoma in a Han Chinese population. Investigative ophthalmology & visual science 27 24854855
2013 Allelic expression analysis of the osteoarthritis susceptibility gene COL11A1 in human joint tissues. BMC musculoskeletal disorders 27 23497244
2003 The transcription factor CCAAT-binding factor CBF/NF-Y regulates the proximal promoter activity in the human alpha 1(XI) collagen gene (COL11A1). The Journal of biological chemistry 27 12805369
2017 Association between COL11A1 (rs1337185) and ADAMTS5 (rs162509) gene polymorphisms and lumbar spine pathologies in Chinese Han population: an observational study. BMJ open 26 28583914
2004 Col11a1 and Col11a2 mRNA expression in the developing mouse cochlea: implications for the correlation of hearing loss phenotype with mutant type XI collagen genotype. Acta oto-laryngologica 26 15141750
2019 The regulation of miR-139-5p on the biological characteristics of breast cancer cells by targeting COL11A1. Mathematical biosciences and engineering : MBE 25 32233587
2022 COL11A1-Driven Epithelial-Mesenchymal Transition and Stemness of Pancreatic Cancer Cells Induce Cell Migration and Invasion by Modulating the AKT/GSK-3β/Snail Pathway. Biomolecules 23 35327583
2022 Berberine inhibits glioma cell migration and invasion by suppressing TGF-β1/COL11A1 pathway. Biochemical and biophysical research communications 23 35944362
2021 Mutant collagen COL11A1 enhances cancerous invasion. Oncogene 23 34584216
2020 COL11A1 Was Involved in Cell Proliferation, Apoptosis and Migration in Non-Small Cell Lung Cancer Cells. Journal of investigative surgery : the official journal of the Academy of Surgical Research 23 33148075
2017 Novel and recurrent COL11A1 and COL2A1 mutations in the Marshall-Stickler syndrome spectrum. Human genome variation 22 28983407
2016 Mutation survey and genotype-phenotype analysis of COL2A1 and COL11A1 genes in 16 Chinese patients with Stickler syndrome. Molecular vision 21 27390512
2024 E2F1 Reduces Sorafenib's Sensitivity of Esophageal Carcinoma Cells via Modulating the miR-29c-3p/COL11A1 Signaling Axis. Current molecular pharmacology 20 36876834
2020 Over-expression of CDX2 alleviates breast cancer by up-regulating microRNA let-7b and inhibiting COL11A1 expression. Cancer cell international 20 31938021
2011 Clinical and molecular analysis of UAE fibrochondrogenesis patients expands the phenotype and reveals two COL11A1 homozygous null mutations. Clinical genetics 20 21668896
2021 miR-335 Restrains the Aggressive Phenotypes of Ovarian Cancer Cells by Inhibiting COL11A1. Cancers 19 34944877
2013 Deletions within COL11A1 in Type 2 stickler syndrome detected by multiplex ligation-dependent probe amplification (MLPA). BMC medical genetics 19 23621912
2003 Auditory function associated with Col11a1 haploinsufficiency in chondrodysplasia (cho) mice. Hearing research 17 12527136
2000 Audiovestibular phenotype associated with a COL11A1 mutation in Marshall syndrome. Archives of otolaryngology--head & neck surgery 17 10889003
2011 Proteomic analysis of Col11a1-associated protein complexes. Proteomics 16 22038862
2024 Genetically inspired organoids prevent joint degeneration and alleviate chondrocyte senescence via Col11a1-HIF1α-mediated glycolysis-OXPHOS metabolism shift. Clinical and translational medicine 15 38314968
2014 A novel dominant COL11A1 mutation resulting in a severe skeletal dysplasia. American journal of medical genetics. Part A 15 25091507
2012 COL11A1 gene is associated with limbus vertebra in gymnasts. International journal of sports medicine 15 22510797
2020 Inherited and de novo biallelic pathogenic variants in COL11A1 result in type 2 Stickler syndrome with severe hearing loss. Molecular genetics & genomic medicine 14 32578940
2019 COL11A1 Polymorphisms Are Associated with Primary Angle-Closure Glaucoma Severity. Journal of ophthalmology 14 30809385
1995 Coding sequence and alternative splicing of the mouse alpha 1(XI) collagen gene (Col11a1). Genomics 14 8530046
2020 Exon-Trapping Assay Improves Clinical Interpretation of COL11A1 and COL11A2 Intronic Variants in Stickler Syndrome Type 2 and Otospondylomegaepiphyseal Dysplasia. Genes 13 33348901
2017 A novel dominant COL11A1 mutation in a child with Stickler syndrome type II is associated with recurrent fractures. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 13 28971234
2005 Isolation of the salmonid rhamnose-binding lectin STL2 from spores of the microsporidian fish parasite Loma salmonae. Journal of fish diseases 13 16159363
1988 Mapping of a human fibrillar collagen gene, pro alpha 1 (XI) (COL11A1), to the p21 region of chromosome 1. Genomics 13 3220479
2020 Multifactor dimensionality reduction reveals a strong gene-gene interaction between STC1 and COL11A1 genes as a possible risk factor of knee osteoarthritis. Molecular biology reports 12 32140959
2022 Association of EFEMP1 with juvenile-onset open angle glaucoma in a patient with concomitant COL11A1-related Stickler syndrome. Ophthalmic genetics 11 35946471
2021 Activation of COL11A1 by PRRX1 promotes tumor progression and radioresistance in ovarian cancer. International journal of radiation biology 11 33970764
2017 A genetic variant in COL11A1 is functionally associated with lumbar disc herniation in Chinese population. Journal of genetics 11 29321344
2021 Collagen XI Alpha 1 (COL11A1) Expression in the Tumor Microenvironment Drives Neuroblastoma Dissemination. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 10 34460335
2013 Nuclear factor Y (NF-Y) regulates the proximal promoter activity of the mouse collagen α1(XI) gene (Col11a1) in chondrocytes. In vitro cellular & developmental biology. Animal 10 24092017
2001 Differential expression of two exons of the alpha1(XI) collagen gene (Col11a1) in the mouse embryo. Matrix biology : journal of the International Society for Matrix Biology 10 11246003
2021 MiR-144-3p inhibits the proliferation, migration and invasion of lung adenocargen cancer cells by targeting COL11A1. Journal of chemotherapy (Florence, Italy) 9 33845716
2021 Mutually Exclusive Expression of COL11A1 by CAFs and Tumour Cells in a Large panCancer and a Salivary Gland Carcinoma Cohort. Head and neck pathology 9 34378164
2017 A mild form of Stickler syndrome type II caused by mosaicism of COL11A1. European journal of medical genetics 9 28315471
2016 Overexpression of α1 chain of type XI collagen (COL11A1) aids in the diagnosis of invasive carcinoma in endoscopically removed malignant colorectal polyps. Pathology, research and practice 9 27021528
2015 Development of novel real-time PCR methodology for quantification of COL11A1 mRNA variants and evaluation in breast cancer tissue specimens. BMC cancer 9 26466668
2015 Sp1 upregulates the proximal promoter activity of the mouse collagen α1(XI) gene (Col11a1) in chondrocytes. In vitro cellular & developmental biology. Animal 9 26487428
2011 A DNA pooling-based case-control study of myopia candidate genes COL11A1, COL18A1, FBN1, and PLOD1 in a Chinese population. Molecular vision 9 21527992
2024 Overexpression of COL11A1 confers tamoxifen resistance in breast cancer. NPJ breast cancer 8 38806505
2022 MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer. Biomaterials science 8 35792605
2021 COL11A1 promotes esophageal squamous cell carcinoma proliferation and metastasis and is inversely regulated by miR-335-5p. Annals of translational medicine 8 34790783
2020 Variable clinical expression of Stickler Syndrome: A case report of a novel COL11A1 mutation. Molecular genetics & genomic medicine 8 32558342
2023 COL11A1-driven positive feedback loop modulates fibroblast transformation and activates pancreatic cancer progression. Cell biology international 7 36861686
2015 A novel COL11A1 mutation affecting splicing in a patient with Stickler syndrome. Human genome variation 7 27081549
2024 Association of genetic variation in COL11A1 with adolescent idiopathic scoliosis. eLife 6 38277211
2022 COL11A1 is Downregulated by miR-339-5p and Promotes Colon Carcinoma Progression. Canadian journal of gastroenterology & hepatology 6 35669376
2021 Association Between COL5a1, COL11a1, and COL11a2 Gene Variations and Rotator Cuff Tendinopathy in Young Athletes. Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine 6 34009784
2021 Hearing Outcomes in Stickler Syndrome: Variation Due to COL2A1 and COL11A1. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 6 34238052
2019 Microarray‑based analysis of COL11A1 and TWIST1 as important differentially‑expressed pathogenic genes between left and right‑sided colon cancer. Molecular medicine reports 6 31545476
2019 Homozygous variants in AMPD2 and COL11A1 lead to a complex phenotype of pontocerebellar hypoplasia type 9 and Stickler syndrome type 2. American journal of medical genetics. Part A 6 31833174
2016 Additional Evidence Supports Association of Common Variants in COL11A1 with Increased Risk of Hip Osteoarthritis Susceptibility. Genetic testing and molecular biomarkers 6 27936936
2021 Novel Mutation in the COL11A1 Gene Causing Marshall-Stickler Syndrome in Three Generations of a Bulgarian Family. Balkan journal of medical genetics : BJMG 5 34447665
2016 A novel COL11A1 missense mutation in siblings with non-ocular Stickler syndrome. Human genome variation 5 27081569
2023 Circular circRANGAP1 Contributes to Non-small Cell Lung Cancer Progression by Increasing COL11A1 Expression Through Sponging miR-653-5p. Biochemical genetics 4 37193942