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Connective Tissue Research Volume 56, 2015 - Issue 5: The tumor microenvironment: the connective tissue/tumor cell/host organ system that modulates tumor progression
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Original Articles

Cripto-1: an extracellular protein – connecting the sequestered biological dots

Malgorzata KlauzinskaTumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA, Correspondence[email protected]
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Daniel BertoletteTumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA,
,
Sudhamsh TippireddyTumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA,
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Luigi StrizziDepartment of Pathology, Program in Cancer Biology and Epigenomics, Stanley Manne Children’s Research Institute at Ann and Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA,
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Peter C. GrayClayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA,
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Monica GonzalesOffice of Research Operations, Office of the Director, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA,
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Meg DurouxLaboratory of Cancer Biology, Biomedicine Group, Department of Health Science and Technology, Aalborg University, Aalborg East, Denmark,
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Menotti RuvoCIRPeB, University of Naples Federico II, Napoli, Italy, ;Istituto di Biostrutture e Bioimmagini del CRN, Napoli, Italy,
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Christian WechselbergerGreiner Bio-One Diagnostics GmbH, Rainbach im Mühlkreis, Austria,
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Nadia P. CastroTumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA,
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Maria Cristina RangelTumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA,
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Annalia FocàIstituto di Biostrutture e Bioimmagini del CRN, Napoli, Italy, ;Dipartimento di Farmacia, University of Naples Federico II, Napoli, Italy, and
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Annamaria SandomenicoCIRPeB, University of Naples Federico II, Napoli, Italy,
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Mary J. C. HendrixProgram in Cancer Biology and Epigenomics, Stanley Manne Children’s Research Institute at Ann and Robert H. Lurie Children’s Hospital of Chicago, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
,
David SalomonTumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA,
&
Frank CuttittaTumor Growth Factor Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA,
show all
Pages 364-380 | Received 27 Apr 2015, Accepted 15 Jul 2015, Published online: 01 Sep 2015
 
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Abstract

Cripto-1 (CR-1) is a multifunctional embryonic protein that is re-expressed during inflammation, wound repair, and malignant transformation. CR-1 can function either as a tethered co-receptor or shed as a free ligand underpinning its flexible role in cell physiology. CR-1 has been shown to mediate cell growth, migration, invasion, and induce epithelial to mesenchymal transition (EMT). The main signaling pathways mediating CR-1 effects include Nodal-dependent (Smad2/3) and Nodal-independent (Src/p44/42/Akt) signaling transduction pathways. In addition, there are several naturally occurring binding partner proteins (BPPs) for CR-1 that can either agonize or antagonize its bioactivity. We will review the collective role of CR-1 as an extracellular protein, discuss caveats to consider in developing a quantitation assay, define possible mechanistic avenues applicable for drug discovery, and report on our experimental approaches to overcome these problematic issues.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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