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This study has successfully demonstrated that exogenous soluble form of CR-1 suppresses the self-renewal of cancer stem cells.
CR-1 expression was evaluated with immunohistochemistry using a tissue microarray on 265 T1-2N0 surgical NSCLC samples. Of the 265 tumors, 250 (94%) expressed various levels of CR-1.
Using molecular dynamics simulations, study demonstrated that Cripto binding to GRP78 completely changes the dynamics of its behavior on the membrane, not allowing GRP78 to disconnect from it, thus enabling GRP78 tumorigenic functions.
Cripto-1 expression is increased by OCT4 overexpression, but decreased by shRNA-mediated OCT4 knockdown. OCT4 overexpression significantly activates Cripto-1 transcriptional activity. A 5'-upstream minimal promoter sequence in the gene-encoding Cripto-1 is significantly activated by OCT4 overexpression.
Targeting the Cripto-1/TAK-1/NF-kappaB/Survivin pathway may be an effective approach to combat apoptosis resistance in cancer.
Knockdown of Cripto-1 inhibits the proliferation, migration, invasion, and angiogenesis in prostate carcinoma cells.
Results identified elevated CR-1 expression in esophageal squamous cell carcinoma (ESCC) specimens which correlated to poor prognosis of the patients. CR-1 high cells isolated from ESCC cells possess cancer stem-like cells (ECSLC) properties.
These results highlight a functional role for CRIPTO and GRP78 in prostate cancer metastasis and suggest that targeting CRIPTO/GRP78 signaling may have significant therapeutic potential.
PGAP6 plays a critical role in Nodal signaling modulation through CRIPTO shedding.
Upregulation of cripto-1 is associated with prostate cancer.
the miR-15b expression is negatively associated with the cripto-1 expression in glioma cells. miR-15b may subsequently impair growth and invasion of glioma cells through targeted regulation of cripto-1.
These findings suggest that CRIPTO expression may be a useful serological marker for diagnostic and/or prognostic purposes during germ cell cancer management.
serum CR-1 is a useful diagnostic and prognostic marker for nonsmall cell lung cancer patients.
Cripto-1 overexpression contributes to aggressiveness and poor prognosis of hepatocellular carcinoma
The main signaling pathways mediating Cripto-1 effects include Nodal-dependent (Smad2/3) and Nodal-independent (Src/p44/42/Akt) signaling transduction pathways
Cripto-1 is a novel and dynamically regulated effector of stem cell functions in colorectal cancer.
these findings suggest a novel molecular network, involving CRIPTO, AKT, and FGFR signaling, in favor of the emergence of mesenchymal-like cancer cells during the development of aggressive prostate tumors.
Report lower gene expression of Cripto in endometriosis but difference not maintained at protein level.
Treatment of U-87 MG cells with CR-1 leads to higher expression of drug efflux protein MDR-1 in the CR-1 positive subpopulation, indicating correlated induction of these two proteins.
These findings clearly suggest that the downregulation of miR-15a-16 with Cripto amplification may be involved in the development of nonsmall cell lung cancer.
Cripto controls the metabolic reprogramming in mouse embryonic stem cell to mouse epiblast stem cell transition.
MEF2C has a role in regulating outflow tract alignment and transcriptional control of Tdgf1
Dissection of the mechanism by which this occurs indicates that mCripto-1 activates receptor activator NF-kappaB/receptor activator NF-kappaB ligand, and NF-kappaB signaling pathways.
our findings strongly suggest that Cripto-1 is a potential driver of mammary tumorigenesis
CR1 protein fragments bind tightly to PfRh4 and also function as soluble inhibitors to block PfRh4 binding to red blood cells and to inhibit the PfRh4-CR1 invasion pathway
Data show that Cripto haploinsufficiency may be associated with increased tumorigenesis, suggesting that the effect of Cripto on tumor development is more complex and may strongly depend on the cellular context.
Cripto is transiently expressed in early differentiating myocardial cells of the left ventricle, right ventricle and outflow tract between late head fold stages and E8.5.
Cripto plays a critical role during mouse gastrulation, especially in mesoderm and endoderm formation
Cripto, a regulator of early embryogenesis, is a novel regulator of muscle regeneration and satellite cell progression toward the myogenic lineage.
These data suggest that Cripto/GRP78 signaling is an important pathway that regulates hematopoietic stem cell quiescence.
Distinct pathways for Nodal and Cripto in the differentiation of visceral endoderm and anterior visceral endoderm from extra-embryonic endoderm stem cells.
These results suggest a differential modulation of CR-1 gene expression in embryonal and colon cancer cells by two different members of the TGF-beta family.
Functional redundancy of the Tdgf1 gene in epiblast and extraembryonic patterning during early mouse embryogenesis is reported.
Data show that hypoxia through HIF-1alpha directly regulates Cripto-1 expression in mouse embryonic stem cells, accelerating and enhancing cardiomyocyte differentiation.
This demonstrates that Smad4-/- and Cripto-/- ES cells favor a neural fate in vitro, but also express the mesodermal phenotype, implying that deletion of either Smad4 or Cripto is not sufficient to block nonneuronal tissue formation.
The regulation of Netrin-1 expression is important in regulating Cripto-1-dependent invasion and migration of mammary epithelial cells.
Cripto can function in trans as an intercellular mediator of Nodal signaling activity.
Cripto facilitates Nodal signaling and inhibits activin signaling by forming receptor complexes with these ligands that are structurally and functionally similar.
two thirds of the Cer1;Cripto double mutants are rescued in processes that are severely compromised in Cripto(-/-) embryos, namely A-P axis orientation, anterior mesendoderm and posterior neuroectoderm formation
Reduced expression of Oep causes the loss of responsiveness to Nodal signals in the prospective ectoderm. Indeed, extending the presence of Oep prolongs the window of competence to respond to Nodal signals.
Late zygotic oep mutants have strongly reduced or absent pitx2 expression in the lateral plate mesoderm (LPM), but this expression can be rescued to strong levels by restoring oep in midline structures only.
Nodal-BMP signaling cascade drives left-right heart morphogenesis by regulating the speed and direction of cardiomyocyte movement
Using mutants in the Nodal receptor cofactor one-eyed pinhead (oep) and the T-box transcription factors spadetail (spt) and no tail (ntl), we were able to define distinctive regulation underlying these sequential phases of PGP midline migration
heterozygote mutations in fgf8, shh or oep lead to a reduced number of ascending dopaminergic neurons in zebrafish and may confer increased susceptibility to the Parkinson disease
Spadetail (T-box gene 16) and one-eyed pintail protein genetically interact and are together essential for the formation of cardiac and somitic mesoderm.
Vg1 and GDF1 signaling require one-eyed pinhead.
Interplay between FGF, one-eyed pinhead (zoep), and T-box transcription factors spt and ntl during zebrafish posterior
Spatial and temporal regulation of FRL1 protein expression during the gastrula stage are demonstrated.
findings show that vegetal cell-specific translational repression of xCR1 mRNA contributes to the spatially restricted accumulation of the xCR1 protein in Xenopus embryos
This gene encodes an epidermal growth factor-related protein that contains a cripto, FRL-1, and cryptic domain. The encoded protein is an extracellular, membrane-bound signaling protein that plays an essential role in embryonic development and tumor growth. Mutations in this gene are associated with forebrain defects. Pseudogenes of this gene are found on chromosomes 2, 3, 6, 8, 19 and X. Alternate splicing results in multiple transcript variants.
cripto-1 growth factor
, epidermal growth factor-like cripto protein CR1
, TERATOCARCINOMA-DERIVED GROWTH FACTOR PRECURSOR (EPIDERMAL GROWTH FACTOR-LIKE CRIPTO PROTEIN) (CRIPTO GROWTH FACTOR)
, cripto growth factor
, epidermal growth factor-like Cripto protein
, teratocarcinoma-derived growth factor
, cryptic protein
, one eyed pinhead
, teratocarcinoma-derived growth factor 1
, fibroblast growth factor receptor ligand 1
, teratocarcinoma-derived growth factor 3