Antibody blockade of the Cripto CFC domain suppresses tumor cell growth in vivo.

@article{Adkins2003AntibodyBO,
  title={Antibody blockade of the Cripto CFC domain suppresses tumor cell growth in vivo.},
  author={Heather B. Adkins and Caterina Bianco and Susan Schiffer and Paul Rayhorn and Mohammad Zafari and Anne E Cheung and Olivia Orozco and Dian L Olson and Antonella De Luca and Ling Ling Chen and Konrad Miatkowski and Christopher D. Benjamin and Nicola Normanno and Kevin P. Williams and Matthew B. Jarpe and Doreen J Lepage and David S Salomon and Michele Sanicola},
  journal={The Journal of clinical investigation},
  year={2003},
  volume={112 4},
  pages={
          575-87
        }
}
Cripto, a cell surface-associated protein belonging to the EGF-CFC family of growth factor-like molecules, is overexpressed in many human solid tumors, including 70-80% of breast and colon tumors, yet how it promotes cell transformation is unclear. During embryogenesis, Cripto complexes with Alk4 via its unique cysteine-rich CFC domain to facilitate signaling by the TGF-beta ligand Nodal. We report, for the first time to our knowledge, that Cripto can directly bind to another TGF-beta ligand… 
Cripto: a novel target for antibody-based cancer immunotherapy.
TLDR
Rat monoclonal antibodies to a Cripto 17-mer peptide, corresponding to the "EGF-like" motif of Cripteo, prevent tumor development in vivo and inhibit the growth of established tumors of LS174T colon xenografts in Scid mice.
Cripto Binds Transforming Growth Factor β (TGF-β) and Inhibits TGF-β Signaling
TLDR
Evidence is provided supporting a novel mechanism in which Cripto inhibits the tumor suppressor function of TGF-β, and targeted disruption of Cripteo expression by use of small inhibitory RNA enhanced T GF-β signaling, indicating that endogenous Cripti plays a role in restraining TGF -β responses.
Cripto Binds Transforming Growth Factor β (TGF-β) and Inhibits TGF-β Signaling
TLDR
Evidence is provided supporting a novel mechanism in which Cripto inhibits the tumor suppressor function of TGF-β, and targeted disruption of Cripteo expression by use of small inhibitory RNA enhanced T GF-β signaling, indicating that endogenous Cripti plays a role in restraining TGF -β responses.
Development of conformational antibodies targeting Cripto-1 with neutralizing effects in vitro.
TLDR
These findings suggest that the selected anti-CFC mAbs have the potential to neutralize the protein oncogenic activity and may be used as theranostic molecules suitable as tumor homing agents for Cripto-1-overexpressing cancer cells and tissues and to overcome drug-resistance in routine cancer therapies.
Role of the EGF-CFC Family in Mammary Gland Development and Neoplasia
TLDR
The multifunction properties of the EGF-CFC family of proteins and the complex network of signaling molecules activated by Cripto-1 focusing in particular on the mammary gland are discussed.
Silencing of FLRG, an antagonist of activin, inhibits human breast tumor cell growth.
TLDR
This work shows that activin-induced growth inhibition is altered in FLRG-expressing breast cancer lines, and provides strong evidence that endogenous FLRG contributes to tumor cell proliferation through antagonizing endogenous activin effects.
Blockade of Cripto binding to cell surface GRP78 inhibits oncogenic Cripto signaling via MAPK/PI3K and Smad2/3 pathways
TLDR
It is shown that targeted disruption of the cell surface Cripto/GRP78 complex using shRNAs or GRP78 immunoneutralization precludes Cripti activation of MAPK/PI3K pathways and modulation ofactivin-A, activin-B, Nodal and transforming growth factor-β1 signaling.
New Insights into Cancer Targeted Therapy: Nodal and Cripto-1 as Attractive Candidates
TLDR
The aim of this review is to clarify the role of CR-1 and Nodal in cancer stem populations and to summarize the current therapeutic strategy to target CSCs using monoclonal antibodies (mAbs) or other molecular tools to interfere with these two proteins.
Cripto as a target for cancer immunotherapy
  • X. Hu, P. Xing
  • Medicine, Biology
    Expert opinion on therapeutic targets
  • 2005
TLDR
The authors review the role of Cripto expression in tumourigenesis and in EMT to promote tumour invasion, with emphasis that the unique EGF-like region ofCripto plays a critical role in Cripti signalling-mediated tumour growth and EMT.
GRP78 and Cripto Form a Complex at the Cell Surface and Collaborate To Inhibit Transforming Growth Factor β Signaling and Enhance Cell Growth
TLDR
It is demonstrated that Cripto and GRP78 interact at the cell surfaces of multiple cell lines and that their interaction is independent of prior association within the ER.
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TLDR
Cripto is released or shed from expressing cells and may serve as an accessible marker gene in the early to mid‐progressive stages of breast and other cancers, and some speculations on possible receptor complexes for Cripto signaling in mammary cells are offered here as a spur to further discoveries.
Cripto-1 Activates Nodal- and ALK4-Dependent and -Independent Signaling Pathways in Mammary Epithelial Cells
TLDR
CR-1 binds to cell surface ALK4 expressed on mammalian epithelial cells in fluorescence-activated cell sorter analysis, as well as by coimmunoprecipitation, suggesting that CR-1 may modulate different signaling pathways to mediate its different functional roles.
Dual Roles of Cripto as a Ligand and Coreceptor in the Nodal Signaling Pathway
TLDR
A model in which Cripto has dual roles as a coreceptor as well as a coligand for Nodal and that this signaling interaction with NodAl is regulated by an unusual form of glycosylation is proposed.
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TLDR
It is demonstrated that breast carcinomas express multiple EGF-related peptides and show that the differential expression of CR-1 in malignant breast epithelial cells may serve as a potential tumour marker for breast cancer.
Cripto Enhances the Tyrosine Phosphorylation of Shc and Activates Mitogen-activated Protein Kinase (MAPK) in Mammary Epithelial Cells*
TLDR
CR-1 can function through a receptor which activates intracellular components in the ras/raf/MEK/MAPK pathway, and was able to increase p42erk-2 mitogen-activated protein kinase (MAPK) activity in HC-11 cells within 5-10 min of treatment.
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TLDR
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Cripto forms a complex with activin and type II activin receptors and can block activin signaling
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  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2003
TLDR
Cripto can form a complex with activin and ActRII/IIB and inhibition of activin signaling provides an additional example of a Cripto effect on the regulation of signaling by transforming growth factor-β superfamily members.
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TLDR
Resistance to TGF-beta and activin is often, but not always, due to reduced expression of the signaling receptor in breast cancer cells, showing that other signal transduction components are functionally intact.
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TLDR
GEO and CBS CRIPTO antisense infectants exhibited a 60 to 70% reduction inCRIPTO protein expression, in monolayer growth and in soft agar cloning efficiency as compared to parental noninfected cells.
The p38 MAPK Pathway Is Required for Cell Growth Inhibition of Human Breast Cancer Cells in Response to Activin*
TLDR
A new role for activin is defined in human breast cancer T47D cells and a new pathway utilized by this growth factor in the mediation of its biological effects in cell growth arrest is highlighted.
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