Affinage

CRIPTO

Protein Cripto · UniProt P13385

Length
188 aa
Mass
21.2 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CRIPTO (TDGF1) is a GPI-anchored, O-fucosylated EGF-CFC family glycoprotein that serves as a multifunctional co-receptor integrating TGF-β superfamily signaling at the cell surface to control embryonic patterning, stem cell maintenance, tissue regeneration, and tumorigenesis. Through its CFC domain, CRIPTO binds the type I receptor ALK4 and is required for Nodal to assemble productive ALK4/ActRIIB complexes that activate Smad2/3 signaling (PMID:11389842, PMID:14581455); it simultaneously antagonizes activin-A/B and TGF-β1 signaling by sequestering these ligands away from their cognate receptor complexes, thereby relieving cytostatic constraints on cell proliferation (PMID:12682303, PMID:17030617). Independent of Nodal/ALK4, CRIPTO engages cell-surface GRP78 to activate c-Src/MAPK/PI3K-Akt and JAK2/STAT3 pathways, promoting epithelial–mesenchymal transition, hematopoietic and mammary stem cell maintenance, and mesenchymal stem cell survival (PMID:21982233, PMID:24749068, PMID:28835002, PMID:15334661). In adult tissues, CRIPTO antagonizes myostatin in satellite cells to drive skeletal muscle regeneration and modulates macrophage plasticity by restraining TGFβ/Smad signaling, with myeloid-specific deletion exacerbating muscular dystrophy (PMID:23129614, PMID:32107853).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 Medium

    Establishing that CRIPTO signals through a novel, non-ErbB receptor to activate MAPK resolved the paradox of CRIPTO-induced ErbB-4 phosphorylation without direct ErbB binding, pointing to an unidentified receptor intermediate.

    Evidence Chemical crosslinking with radiolabeled CRIPTO and ErbB-4 blocking antibody/ribozyme knockdown in mammary epithelial cells

    PMID:10085099

    Open questions at the time
    • The 130 kDa and 60 kDa binding species were not molecularly identified
    • Mechanism by which ErbB-4 is indirectly activated remains unclear
  2. 2000 High

    Demonstrating GPI anchorage of CRIPTO established its membrane-tethered topology, explaining how a protein lacking a transmembrane domain operates as a cell-surface co-receptor.

    Evidence PI-PLC treatment, immunofluorescence, and biochemical fractionation

    PMID:10640699

    Open questions at the time
    • Whether GPI anchorage is required for signaling activity was not tested
  3. 2001 High

    Identification of the CFC domain as the interface for ALK4 binding, and demonstration that this interaction is required for Nodal to engage the ALK4/ActRIIB complex and activate Smad2, defined CRIPTO's core co-receptor mechanism.

    Evidence Reciprocal co-immunoprecipitation, receptor binding assays, and Smad2 phosphorylation assays

    PMID:11389842

    Open questions at the time
    • Structural basis of CFC–ALK4 interaction not resolved at atomic level
    • Whether CRIPTO contacts Nodal and ALK4 simultaneously was not demonstrated
  4. 2002 High

    Showing that O-linked fucosylation is essential for Nodal binding and signaling revealed a post-translational modification requirement that gates CRIPTO co-receptor competence.

    Evidence Glycosylation site mutants tested in luciferase reporter and cell co-culture signaling assays

    PMID:12052855

    Open questions at the time
    • The fucosyltransferase responsible was not identified in this study
    • Whether fucosylation affects other CRIPTO ligand interactions was untested
  5. 2003 High

    Discovery that CRIPTO simultaneously promotes Nodal signaling and antagonizes activin signaling—by binding activin and blocking its ALK4/ActRII assembly—revealed a dual agonist/antagonist logic governing TGF-β pathway selectivity.

    Evidence Chemical crosslinking, co-immunoprecipitation, and luciferase reporter assays across HepG2 and 293T cells; antibody blocking of CFC domain

    PMID:12682303 PMID:12925698

    Open questions at the time
    • Stoichiometry and competitive binding kinetics between Nodal and activin for CRIPTO were not quantified
  6. 2003 High

    Epistasis experiments placing CRIPTO upstream of ALK4 in cardiomyogenesis established its role as an obligate Nodal pathway component during lineage commitment.

    Evidence Rescue of Cripto-null ES cell differentiation defect by constitutively active ALK4

    PMID:14581455

    Open questions at the time
    • Whether CRIPTO has ALK4-independent roles in cardiac specification was not addressed
  7. 2004 Medium

    Linking CRIPTO overexpression to a full EMT program (E-cadherin loss, N-cadherin/vimentin/Snail gain) through c-Src identified CRIPTO as a driver of mesenchymal conversion independent of canonical TGF-β/Smad signaling.

    Evidence Src inhibitor PP2, migration assays, and EMT marker profiling by Western blot

    PMID:15334661

    Open questions at the time
    • The receptor mediating c-Src activation was not identified
    • In vivo relevance of CRIPTO-driven EMT not demonstrated in this study
  8. 2006 High

    Demonstrating that CRIPTO directly binds TGF-β1 and blocks its engagement with TβRI extended the antagonism model beyond activins, establishing CRIPTO as a broad suppressor of growth-inhibitory TGF-β superfamily signaling.

    Evidence Binding assays, Smad phosphorylation, siRNA knockdown of endogenous CRIPTO in mammary epithelial cells

    PMID:17030617

    Open questions at the time
    • Whether CRIPTO antagonizes other TGF-β isoforms (TGF-β2, TGF-β3) was not tested
  9. 2007 High

    Proving that GPI anchorage is required for trans (paracrine) Nodal co-receptor activity resolved how a GPI-linked protein without a cytoplasmic domain organizes signaling complexes on opposing cells.

    Evidence Truncation mutants, transmembrane chimeras, and PI-PLC treatment with luciferase reporter readout

    PMID:17925387

    Open questions at the time
    • Mechanism of trans-signaling across cell membranes by a GPI-linked protein remains structurally unresolved
  10. 2008 High

    Showing that CRIPTO recruits Furin/PACE4 and couples Nodal precursor processing to endocytosis in Flotillin-positive membrane microdomains revealed a trafficking-dependent mechanism that integrates ligand maturation with receptor activation.

    Evidence Co-immunoprecipitation with Furin/PACE4, density gradient fractionation, confocal microscopy of Flotillin compartments, brefeldin A block

    PMID:18772886

    Open questions at the time
    • Whether endocytosis is strictly required for signaling output was not tested by endocytosis-blocking mutants
  11. 2009 Medium

    NMR determination of CFC domain topology and SPR measurement of micromolar-affinity ALK4 binding provided the first structural framework for the CRIPTO co-receptor interface.

    Evidence NMR spectroscopy, surface plasmon resonance, molecular docking validated against prior mutagenesis

    PMID:19035567

    Open questions at the time
    • No co-crystal structure of CFC–ALK4 complex exists
    • Full-length CRIPTO structure remains undetermined
  12. 2011 High

    Identification of GRP78 as a cell-surface CRIPTO receptor on hematopoietic stem cells, mediating quiescence via metabolic reprogramming under hypoxia, established a Nodal/ALK4-independent signaling axis in the bone marrow niche.

    Evidence GRP78 blocking antibody, HIF-1α knockout mice, HSC transplantation and metabolic assays

    PMID:21982233

    Open questions at the time
    • How CRIPTO–GRP78 engagement is transduced to intracellular kinases was not fully defined
    • Whether this pathway operates in non-hematopoietic stem niches was unknown
  13. 2012 High

    Demonstrating that CRIPTO antagonizes myostatin in satellite cells to promote muscle regeneration established an adult tissue-repair function and expanded the range of TGF-β ligands controlled by CRIPTO.

    Evidence Satellite cell-specific conditional knockout and gain-of-function in muscle injury models

    PMID:23129614

    Open questions at the time
    • Whether CRIPTO binds myostatin directly or acts indirectly through shared receptors was not resolved
  14. 2014 High

    Showing that CRIPTO/GRP78 maintains both fetal and adult mammary stem cells, with GRP78 conditional deletion abolishing reconstitution potential, validated the GRP78 axis as a general stem cell maintenance pathway.

    Evidence Mammary gland reconstitution assay, GRP78 conditional knockout, CRIPTO antagonist treatment

    PMID:24749068

    Open questions at the time
    • Downstream effectors of GRP78 in mammary stem cells were not fully mapped
  15. 2018 Medium

    Defining JAK2/STAT3 as the intracellular cascade downstream of CRIPTO–GRP78 in mesenchymal stem cells provided a specific signaling pathway linking this receptor pair to proliferation and survival.

    Evidence Anti-GRP78 blocking antibody, STAT3 and BCL3 siRNA, Western blot for pathway components

    PMID:28835002

    Open questions at the time
    • How GRP78 activates JAK2 mechanistically is unknown
    • Whether JAK2/STAT3 mediates all GRP78-dependent CRIPTO functions is untested
  16. 2020 High

    Myeloid-specific Cripto deletion revealed that CRIPTO restrains TGFβ/Smad signaling in macrophages to enable anti-inflammatory polarization, linking CRIPTO to immune cell plasticity and dystrophic muscle pathology.

    Evidence Conditional myeloid-specific Cripto knockout in mdx dystrophy model, TGFβ/Smad signaling and vascular remodeling analysis

    PMID:32107853

    Open questions at the time
    • Whether CRIPTO acts on macrophages via GRP78 or another receptor in this context is unknown
    • Relevance to non-dystrophic inflammatory conditions untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of CRIPTO's simultaneous engagement with multiple TGF-β ligands and receptors, the precise mechanism coupling GRP78 binding to intracellular kinase activation, and whether extracellular vesicle-associated CRIPTO constitutes a physiologically significant signaling mode remain unresolved.
  • No co-crystal structure of any CRIPTO–ligand–receptor ternary complex
  • GRP78-to-JAK2 signal transduction mechanism undefined
  • EV-associated CRIPTO function demonstrated only in one in vitro system

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 4 GO:0048018 receptor ligand activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 2
Partners
ACVR2BALK4FURINGRP78NODALPACE4TGFB1
Complex memberships
Nodal/CRIPTO/ALK4/ActRIIB signaling complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Cripto interacts with the type I receptor ALK4 via its conserved CFC motif, and this interaction is necessary for Nodal binding to the ALK4/ActR-IIB receptor complex and for Smad2 activation by Nodal. Co-immunoprecipitation, receptor binding assays, Smad2 phosphorylation assays in cell culture Molecular cell High 11389842
2002 Cripto functions as both a coreceptor and a coligand (secreted signaling factor) for Nodal, and its ability to bind Nodal and mediate Nodal signaling requires O-linked fucosylation at a conserved site within EGF-CFC proteins. Luciferase reporter assay, cell coculture assays, glycosylation mutant analysis Molecular and cellular biology High 12052855
2000 Cripto protein is anchored to the plasma membrane via a glycosylphosphatidylinositol (GPI) moiety, as demonstrated by immunofluorescence and biochemical characterization. Immunofluorescence, biochemical fractionation, PI-PLC treatment Mechanisms of development High 10640699
2003 Cripto can form a complex with activin and ActRII/IIB receptors, and inhibits activin signaling by blocking the association of ALK4 with ActRII/IIB; Cripto can simultaneously facilitate Nodal signaling while antagonizing activin signaling. Chemical crosslinking, co-immunoprecipitation, luciferase reporter assays in HepG2 and 293T cells Proceedings of the National Academy of Sciences of the United States of America High 12682303
2003 Cripto directly binds Activin B via its CFC domain, and overexpression blocks Activin B-induced growth suppression of breast cancer cells; anti-CFC domain antibody disrupts both Cripto-Nodal and Cripto-Activin B interactions by blocking CFC domain association with ALK4 or Activin B. Binding assays, cell proliferation assays, antibody blocking experiments, xenograft tumor models The Journal of clinical investigation High 12925698
2003 Cripto-dependent Nodal/Cripto/Alk4 (ActRIB) signaling activates the Smad2 pathway and is required for cardiomyogenesis in embryonic stem cells; constitutively active ActRIB compensates for lack of Cripto, placing Cripto upstream of Alk4 in this pathway. ES cell differentiation assays, Smad2 activation assays, genetic rescue with constitutively active ActRIB, Nodal antagonist treatment The Journal of cell biology High 14581455
2006 Cripto binds TGF-β1 directly and reduces association of TGF-β with its type I receptor TβRI, thereby suppressing TGF-β signaling and its cytostatic effects in mammary epithelial cells; siRNA knockdown of Cripto enhances TGF-β signaling, confirming endogenous Cripto restrains TGF-β responses. Binding assays, Smad phosphorylation assays, siRNA knockdown, cell proliferation assays Molecular and cellular biology High 17030617
2007 GPI anchorage of Cripto-1 is required for its paracrine (trans) activity as a Nodal co-receptor; soluble truncated forms and transmembrane forms show significantly reduced ability to induce Nodal signaling compared to GPI-anchored Cripto; PI-PLC treatment removes cell-surface Cripto and renders cells refractory to Nodal stimulation. Fluorescent cell-labeling, immunofluorescence, PI-PLC treatment, luciferase reporter assay with truncation mutants The Journal of biological chemistry High 17925387
2008 Cripto binds the proprotein convertases Furin and PACE4 and localizes Nodal precursor processing at the cell surface; Cripto and uncleaved Nodal associate during secretion; Cripto guides the Nodal precursor in detergent-resistant membranes to endocytic microdomains marked by Flotillin, coupling Nodal processing and endocytosis. Co-immunoprecipitation, density gradient fractionation, antibody uptake experiments, brefeldin A treatment, confocal microscopy The EMBO journal High 18772886
1999 Cripto-1 does not bind directly to ErbB receptors but indirectly induces tyrosine phosphorylation of ErbB-4; chemical crosslinking identifies two specific Cripto-1 binding bands of 130 kDa and 60 kDa on mammary epithelial cell membranes, suggesting a novel receptor; functional ErbB-4 is required for Cripto-1-induced MAPK activation. Chemical crosslinking with 125I-Cripto-1, anti-ErbB-4 blocking antibody, hammerhead ribozyme knockdown of ErbB-4, tyrosine phosphorylation assays The Journal of biological chemistry Medium 10085099
2005 Cripto-1 activates c-Src/PI3K/Akt and Ras/MAPK intracellular pathways through a Nodal/Alk4-independent mechanism that involves binding to the cell surface heparan sulfate proteoglycan glypican-1. Cell signaling assays, pathway inhibitor studies (review summarizing experimental findings) Oncogene Medium 16123806
2011 Cripto signals through cell surface receptor GRP78 to regulate hematopoietic stem cell quiescence in the hypoxic bone marrow niche; Cripto/GRP78 signaling induces higher glycolytic activity and lower mitochondrial potential in HSCs; HIF-1α regulates Cripto expression in the endosteal niche. Flow cytometry, transplantation assays, in vitro HSC culture with Cripto, HIF-1α knockout mice, GRP78 blocking antibody Cell stem cell High 21982233
2004 Cripto-1 overexpression promotes epithelial-mesenchymal transition, decreasing E-cadherin and increasing N-cadherin, vimentin, Snail, cyclin-D1, and activating c-Src, FAK, Akt, GSK-3β, and β-catenin; c-Src inhibitor PP2 reduces phosphorylation of these downstream mediators and impairs CR-1-enhanced cell migration. Western blot, immunohistochemistry, Src inhibitor (PP2) treatment, wound-healing/Boyden chamber migration assays Journal of cellular physiology Medium 15334661
2014 CRIPTO/GRP78 signaling maintains fetal and adult mammary stem cells ex vivo; surface GRP78 marks CRIPTO-responsive stem cell-enriched populations; deletion of GRP78 from mammary epithelial cells blocks their mammary gland reconstitution potential. Mammary gland reconstitution assay, GRP78 conditional knockout, CRIPTO antagonist treatment, ex vivo culture Stem cell reports High 24749068
2012 Cripto regulates skeletal muscle regeneration and satellite cell determination by antagonizing the TGF-β ligand myostatin; conditional inactivation of Cripto in adult satellite cells compromises regeneration, while gain-of-function accelerates regeneration and leads to muscle hypertrophy. Conditional knockout (satellite cell-specific Cripto deletion), gain-of-function overexpression, muscle injury models, myostatin antagonism assays Proceedings of the National Academy of Sciences of the United States of America High 23129614
2007 Expression of the short form of human Cripto-1 is directly regulated at the transcriptional level by the canonical Wnt/β-catenin/TCF signaling pathway through an intronic-exonic enhancer element containing three tandem TCF/LEF binding sites. Luciferase reporter assay with TCF/LEF binding site mutations, chromatin-based analysis Biochemical and biophysical research communications Medium 17291450
2009 The CFC domain of human Cripto interacts with the ALK4 receptor with a KD in the micromolar range; NMR analysis shows the CFC domain topology is determined by three disulfide bridges, and residues H120 and W124 are externally exposed and contribute to ALK4 binding as identified by molecular docking consistent with prior mutagenesis data. NMR spectroscopy, surface plasmon resonance (SPR), molecular docking Journal of peptide science Medium 19035567
2016 MEF2C directly regulates transcription of Tdgf1 (Cripto) in the anterior second heart field via an AHF-restricted Tdgf1 enhancer; loss of Mef2c in the AHF leads to outflow tract alignment defects and reduced Cripto expression. Conditional knockout of Mef2c in AHF, Tdgf1 enhancer reporter assay, ChIP-like enhancer analysis Development (Cambridge, England) Medium 26811383
2010 Cripto-1 expression in NTERA2/D1 embryonal carcinoma cells is regulated by a Smad2/3-dependent autocrine loop, by Oct4/Nanog transcription factors, and partially by DNA methylation status of the promoter region. siRNA knockdown of Smad2/3, Oct4, Nanog; promoter methylation analysis; luciferase reporter assay Stem cells (Dayton, Ohio) Medium 20549704
2020 Cripto in muscle-infiltrating macrophages is required for anti-inflammatory CD206+ macrophage expansion during regeneration; conditional deletion of Cripto in the myeloid lineage causes aberrant TGFβ/Smad signaling activation in macrophages, impairs macrophage plasticity, increases Endothelial-to-Mesenchymal Transition (EndMT), and exacerbates muscular dystrophy. Conditional myeloid-specific Cripto knockout (CriptoMy-LOF), mdx model, TGFβ/Smad signaling assays, vascular remodeling analysis EMBO reports High 32107853
2016 Cripto-1 activates NF-κB signaling in macrophages by inducing IκB kinase phosphorylation and p65 nuclear translocation, enhancing cytokine secretion and phagocytic activity; NF-κB inhibitor blocks these Cripto-1-induced effects. Stable Cripto-1 overexpressing cell line, macrophage conditioning assays, NF-κB inhibitor (PDTC) treatment, Western blot for IκB kinase and p65 Immunologic research Medium 26476731
2013 Conditional inactivation of Cripto during gastrulation results in accumulation of mesenchymal cells around the primitive streak and defects in mesoderm and definitive endoderm formation; both the Fgf8-Fgfr1 pathway and p38 MAP kinase activation are partially affected by loss of Cripto. Conditional Cripto knockout during gastrulation, embryo phenotyping, pathway analysis (Fgf8-Fgfr1, p38 MAPK) Developmental biology Medium 23747598
2022 CRIPTO is present on both small and large extracellular vesicles (EVs) released by teratocarcinoma cells; large EVs containing CRIPTO specifically impair migration of glioblastoma recipient cells without affecting proliferation or drug sensitivity. Differential centrifugation EV isolation, Western blot, nanoparticle tracking analysis, cell migration assays Cancers Medium 35954365
2018 Cripto enhances proliferation and survival of mesenchymal stem cells by activating the JAK2/STAT3 pathway in a GRP78-dependent manner; anti-GRP78 antibody blocks Cripto-induced p-JAK2, p-STAT3, c-Myc, cyclin D1, and BCL3 upregulation. Anti-GRP78 blocking antibody, STAT3 siRNA, BCL3 siRNA, Western blot for pathway components, proliferation/apoptosis assays Biomolecules & therapeutics Medium 28835002

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms. Molecular cell 317 11389842
2002 Dual roles of Cripto as a ligand and coreceptor in the nodal signaling pathway. Molecular and cellular biology 175 12052855
1992 Differential immunohistochemical detection of amphiregulin and cripto in human normal colon and colorectal tumors. Cancer research 146 1596904
2003 Cripto forms a complex with activin and type II activin receptors and can block activin signaling. Proceedings of the National Academy of Sciences of the United States of America 139 12682303
2003 Antibody blockade of the Cripto CFC domain suppresses tumor cell growth in vivo. The Journal of clinical investigation 138 12925698
2011 Cripto regulates hematopoietic stem cells as a hypoxic-niche-related factor through cell surface receptor GRP78. Cell stem cell 136 21982233
2005 Cripto-1: a multifunctional modulator during embryogenesis and oncogenesis. Oncogene 136 16123806
2003 Nodal-dependent Cripto signaling promotes cardiomyogenesis and redirects the neural fate of embryonic stem cells. The Journal of cell biology 136 14581455
2004 Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-Cripto-1 transgenic mice. Journal of cellular physiology 114 15334661
2000 Membrane-anchorage of Cripto protein by glycosylphosphatidylinositol and its distribution during early mouse development. Mechanisms of development 100 10640699
2012 Role of Cripto-1 during epithelial-to-mesenchymal transition in development and cancer. The American journal of pathology 88 22542493
2002 A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects. Human genetics 85 12073012
2006 Cripto binds transforming growth factor beta (TGF-beta) and inhibits TGF-beta signaling. Molecular and cellular biology 80 17030617
2023 A review of chromium (Cr) epigenetic toxicity and health hazards. The Science of the total environment 79 37075992
2006 Reduction of Cr(VI) by a Bacillus sp. Biotechnology letters 79 16555008
2001 Non-oxidative mechanisms are responsible for the induction of mutagenesis by reduction of Cr(VI) with cysteine: role of ternary DNA adducts in Cr(III)-dependent mutagenesis. Biochemistry 79 11148050
2010 Bioremediation of Cr(VI) and immobilization as Cr(III) by Ochrobactrum anthropi. Environmental science & technology 77 20608725
2002 Molecular mechanisms of Cr(VI)-induced carcinogenesis. Molecular and cellular biochemistry 77 12162446
2001 Cripto-1 enhances migration and branching morphogenesis of mouse mammary epithelial cells. Experimental cell research 77 11339828
2012 Cripto/GRP78 modulation of the TGF-β pathway in development and oncogenesis. FEBS letters 73 22306319
2006 Identification of cripto-1 as a novel serologic marker for breast and colon cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 70 16951234
2008 Cripto recruits Furin and PACE4 and controls Nodal trafficking during proteolytic maturation. The EMBO journal 69 18772886
2005 Role of human cripto-1 in tumor angiogenesis. Journal of the National Cancer Institute 66 15657343
2002 Transforming growth factor alpha, amphiregulin and cripto-1 are frequently expressed in advanced human ovarian carcinomas. International journal of oncology 65 12370739
1999 Cripto: a novel epidermal growth factor (EGF)-related peptide in mammary gland development and neoplasia. BioEssays : news and reviews in molecular, cellular and developmental biology 65 10070255
1999 Cripto-1 indirectly stimulates the tyrosine phosphorylation of erb B-4 through a novel receptor. The Journal of biological chemistry 65 10085099
2005 Cripto-1: an oncofetal gene with many faces. Current topics in developmental biology 64 15949532
2004 Cripto-1 overexpression leads to enhanced invasiveness and resistance to anoikis in human MCF-7 breast cancer cells. Journal of cellular physiology 58 14584041
2002 Cripto: a tumor growth factor and more. Journal of cellular physiology 58 11857442
2002 Critical role of chromium (Cr)-DNA interactions in the formation of Cr-induced polymerase arresting lesions. Biochemistry 58 12369844
2018 Mechanisms of Cr(VI) resistance by endophytic Sphingomonas sp. LK11 and its Cr(VI) phytotoxic mitigating effects in soybean (Glycine max L.). Ecotoxicology and environmental safety 55 30170313
1991 Expression of cripto, a novel gene of the epidermal growth factor family, in human gastrointestinal carcinomas. Japanese journal of cancer research : Gann 55 1938601
2019 Mechanisms of Cr(VI) reduction by Bacillus sp. CRB-1, a novel Cr(VI)-reducing bacterium isolated from tannery activated sludge. Ecotoxicology and environmental safety 54 31629191
2021 Bioreduction performances and mechanisms of Cr(VI) by Sporosarcina saromensis W5, a novel Cr(VI)-reducing facultative anaerobic bacteria. Journal of hazardous materials 53 33609863
2008 Emerging roles of nodal and Cripto-1: from embryogenesis to breast cancer progression. Breast disease 53 19029628
2014 cC1qR/CR and gC1qR/p33: observations in cancer. Molecular immunology 52 25044096
2022 MRD in multiple myeloma: does CR really matter? Blood 51 35560160
2013 Cr(VI) Formation related to Cr(III)-muscovite and birnessite interactions in ultramafic environments. Environmental science & technology 51 23952582
2011 An evolving web of signaling networks regulated by Cripto-1. Growth factors (Chur, Switzerland) 50 22149969
2010 Cripto-1 is a cell surface marker for a tumorigenic, undifferentiated subpopulation in human embryonal carcinoma cells. Stem cells (Dayton, Ohio) 50 20549704
2007 Requirement of glycosylphosphatidylinositol anchor of Cripto-1 for trans activity as a Nodal co-receptor. The Journal of biological chemistry 50 17925387
2005 Nodal-dependant Cripto signaling in ES cells: from stem cells to tumor biology. Oncogene 50 16123800
2022 Natural source of Cr(VI) in soil: The anoxic oxidation of Cr(III) by Mn oxides. Journal of hazardous materials 49 35381512
2018 A novel interaction between CX3CR1 and CCR2 signalling in monocytes constitutes an underlying mechanism for persistent vincristine-induced pain. Journal of neuroinflammation 49 29625610
2015 Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer. Cell death and differentiation 49 26343543
2010 Cripto-1: an embryonic gene that promotes tumorigenesis. Future oncology (London, England) 49 20624125
2000 Cripto-1-induced increase in vimentin expression is associated with enhanced migration of human Caski cervical carcinoma cells. Experimental cell research 48 10854071
2016 MEF2C regulates outflow tract alignment and transcriptional control of Tdgf1. Development (Cambridge, England) 47 26811383
2002 Biochemical responses of Cr-tolerant and Cr-sensitive mung bean cultivars grown on varying levels of chromium. Chemosphere 47 12137039
2014 CRIPTO/GRP78 signaling maintains fetal and adult mammary stem cells ex vivo. Stem cell reports 46 24749068
1978 The haemolytic action of particulate metals (Cd, Cr, Co, Fe, Mo, Ni, Ta, Ti, Zn, Co-Cr alloy). The Journal of pathology 46 722392
1996 Detection of amphiregulin and Cripto-1 in mammary tumors from transgenic mice. Molecular carcinogenesis 44 8561865
1998 Cripto: roles in mammary cell growth, survival, differentiation and transformation. Cell death and differentiation 42 10200494
2011 Regulation of extra-embryonic endoderm stem cell differentiation by Nodal and Cripto signaling. Development (Cambridge, England) 41 21862554
2008 Potential for cripto-1 in defining stem cell-like characteristics in human malignant melanoma. Cell cycle (Georgetown, Tex.) 41 18604175
2012 Cripto regulates skeletal muscle regeneration and modulates satellite cell determination by antagonizing myostatin. Proceedings of the National Academy of Sciences of the United States of America 40 23129614
1976 Macrophage requirements of CR- and CR+ B lymphocytes for antibody production in vitro. Journal of immunology (Baltimore, Md. : 1950) 35 1083874
2022 Observation of Néel-type skyrmions in acentric self-intercalated Cr1+δTe2. Nature communications 32 35803924
2003 Characterization of nonmutagenic Cr(III)-DNA interactions. Chemical research in toxicology 30 12870887
2017 CoQ10 Deficiency May Indicate Mitochondrial Dysfunction in Cr(VI) Toxicity. International journal of molecular sciences 29 28441753
2007 beta-Catenin/TCF/LEF regulate expression of the short form human Cripto-1. Biochemical and biophysical research communications 29 17291450
2005 Context-dependent neuronal differentiation and germ layer induction of Smad4-/- and Cripto-/- embryonic stem cells. Molecular and cellular neurosciences 29 15737733
2003 Decrypting the role of Cripto in tumorigenesis. The Journal of clinical investigation 29 12925690
2018 CRIPTO promotes an aggressive tumour phenotype and resistance to treatment in hepatocellular carcinoma. The Journal of pathology 28 29604056
2014 Cripto-1 expression in glioblastoma multiforme. Brain pathology (Zurich, Switzerland) 28 24521322
2009 Riding shotgun: a dual role for the epidermal growth factor-Cripto/FRL-1/Cryptic protein Cripto in Nodal trafficking. Traffic (Copenhagen, Denmark) 28 19302412
2012 Hematopoietic stem cells are regulated by Cripto, as an intermediary of HIF-1α in the hypoxic bone marrow niche. Annals of the New York Academy of Sciences 26 22901256
2018 Cripto Enhances Proliferation and Survival of Mesenchymal Stem Cells by Up-Regulating JAK2/STAT3 Pathway in a GRP78-Dependent Manner. Biomolecules & therapeutics 25 28835002
2021 Fractalkine/CX3CR1 Pathway in Neuropathic Pain: An Update. Frontiers in pain research (Lausanne, Switzerland) 23 35295489
2020 Exploring novel Cr(VI) remediation genes for Cr(VI)-contaminated industrial wastewater treatment by comparative metatranscriptomics and metagenomics. The Science of the total environment 23 32623159
1996 Characterization of the mouse Tdgf1 gene and Tdgf pseudogenes. Mammalian genome : official journal of the International Mammalian Genome Society 23 8661720
2016 Cripto-1 modulates macrophage cytokine secretion and phagocytic activity via NF-κB signaling. Immunologic research 22 26476731
2014 MiR-15a-16 represses Cripto and inhibits NSCLC cell progression. Molecular and cellular biochemistry 22 24500260
2011 The Response of Shewanella oneidensis MR-1 to Cr(III) Toxicity Differs from that to Cr(VI). Frontiers in microbiology 22 22125549
2001 Identification of Cripto-1 in human milk. Breast cancer research and treatment 22 11368405
2013 The significance of a Cripto-1 positive subpopulation of human melanoma cells exhibiting stem cell-like characteristics. Cell cycle (Georgetown, Tex.) 21 23574716
2022 Epigenetic alterations of CXCL5 in Cr(VI)-induced carcinogenesis. The Science of the total environment 20 35660107
2019 Fidelity of a PDX-CR model for bladder cancer. Biochemical and biophysical research communications 20 31303270
2013 Nodal/Cripto signaling in fetal male germ cell development: implications for testicular germ cell tumors. The International journal of developmental biology 20 23784832
2023 Alleviation of Hg-, Cr-, Cu-, and Zn-Induced Heavy Metals Stress by Exogenous Sodium Nitroprusside in Rice Plants. Plants (Basel, Switzerland) 19 36986987
2020 Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle. EMBO reports 19 32107853
2012 Bacterial diversity in Cr(VI) and Cr(III)-contaminated industrial wastewaters. Extremophiles : life under extreme conditions 19 22258276
2014 Cytogenomics of hexavalent chromium (Cr 6+) exposed cells: a comprehensive review. The Indian journal of medical research 18 24820829
2014 The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis. BMC biotechnology 18 25077436
2012 Studies on the genotoxic effect of chromium oxide (Cr VI): interaction with deoxyribonucleic acid in solution. Mutation research 18 23098859
2009 Teratocarcinoma-derived growth factor 1 (TDGF1) sequence variants in patients with congenital heart defect. International journal of cardiology 18 19853938
2019 Development of conformational antibodies targeting Cripto-1 with neutralizing effects in vitro. Biochimie 17 30703478
2011 Altered expression of activin, cripto, and follistatin in the endometrium of women with endometrioma. Fertility and sterility 17 21496809
2008 Environmental and kinetic parameters for Cr(VI) bioreduction by a bacterial monoculture purified from Cr(VI)-resistant consortium. Biological trace element research 17 18317706
2023 CX3CR1+ Macrophage Facilitates the Resolution of Allergic Lung Inflammation via Interacting CCL26. American journal of respiratory and critical care medicine 16 36790376
2010 Toxic effects of Cr(VI) and Cr(III) on energy metabolism of heterotrophic Euglena gracilis. Aquatic toxicology (Amsterdam, Netherlands) 16 20851473
1999 Expression of cripto and amphiregulin in colon mucosa from high risk colon cancer families. International journal of oncology 16 10024674
2020 Efficient reduction of reactive black 5 and Cr(Ⅵ) by a newly isolated bacterium of Ochrobactrum anthropi. Journal of hazardous materials 15 33321321
2013 Cripto is required for mesoderm and endoderm cell allocation during mouse gastrulation. Developmental biology 15 23747598
2022 A Novel Localization in Human Large Extracellular Vesicles for the EGF-CFC Founder Member CRIPTO and Its Biological and Therapeutic Implications. Cancers 14 35954365
2021 Cripto-1 as a Key Factor in Tumor Progression, Epithelial to Mesenchymal Transition and Cancer Stem Cells. International journal of molecular sciences 14 34502188
2014 Expression of Nodal, Cripto, SMAD3, phosphorylated SMAD3, and SMAD4 in the proliferative endometrium of women with endometriosis. Reproductive sciences (Thousand Oaks, Calif.) 14 25228630
2013 Quantitative proteome analysis of overexpressed Cripto-1 tumor cell reveals 14-3-3γ as a novel biomarker in nasopharyngeal carcinoma. Journal of proteomics 14 23500129
2011 Human recombinant Cripto-1 increases doubling time and reduces proliferation of HeLa cells independent of pro-proliferation pathways. Cancer letters 14 22182448
2009 Structural insights into the interaction between the Cripto CFC domain and the ALK4 receptor. Journal of peptide science : an official publication of the European Peptide Society 14 19035567